The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index; 38 of the 46 sources its claims cite were checked for support.
Targeting immune–fibroblast cell communication in heart failure
Open accessPublished version of a preprint
Abstract
Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction 1,2. However, the molecular mechanisms driving immune-fibroblast cell communication in human cardiac disease remain unexplored and there are at present no approved treatments that directly target cardiac fibrosis 3,4. Here we performed multiomic single-cell gene expression, epitope mapping and chromatin accessibility profiling in 45 healthy donor, acutely infarcted and chronically failing human hearts. We identified a disease-associated fibroblast trajectory that diverged into distinct populations reminiscent of myofibroblasts and matrifibrocytes, the latter expressing fibroblast activator protein (FAP) and periostin (POSTN). Genetic lineage tracing of FAP+ fibroblasts in vivo showed that they contribute to the POSTN lineage but not the myofibroblast lineage. We assessed the applicability of experimental systems to model cardiac fibroblasts and demonstrated that three different in vivo mouse models of cardiac injury were superior compared with cultured human heart and dermal fibroblasts in recapitulating the human disease phenotype. Ligand-receptor analysis and spatial transcriptomics predicted that interactions between C-C chemokine receptor type 2 (CCR2) macrophages and fibroblasts mediated by interleukin-1β (IL-1β) signalling drove the emergence of FAP/POSTN fibroblasts within spatially defined niches. In vivo, we deleted the IL-1 receptor on fibroblasts and the IL-1β ligand in CCR2+ monocytes and macrophages, and inhibited IL-1β signalling using a monoclonal antibody, and showed reduced FAP/POSTN fibroblasts, diminished myocardial fibrosis and improved cardiac function. These findings highlight the broader therapeutic potential of targeting inflammation to treat tissue fibrosis and preserve organ function.
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Claims the paper makes
97 Own result · 19 Own method · 17 Own interpretation · 10 Partly supported · 8 Supported · 2 No full text of the sources · 1 Supported so far · 1 Mixed support · 1 Couldn’t confirm · 1 No basis given · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“However, these studies rely on nuclear RNA information and lack cellular transcriptomic, epigenetic and proteomic profiling information necessary to obtain a granular picture of the precise immune and fibroblast populations that emerge in the failing human heart and collaborate to drive cardiac fibrosis.”
§ Targeting immune–fibroblast cell communication in heart failure > Abstract
What the sources say
- Not checked — no full text of the sourcecites [18] Tucker, N. R. et al. Transcriptional and cellular diversity of the human heart. Circulation 142, 466–482 (2020). source
- Partly supportedcites [19] Chaffin, M. et al. Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy. Nature https://doi.org/10.1038/S41586-022-04817-8 (2022). sourceExperimental — accuracy not yet measured
The Methods describe single-nucleus RNA sequencing, supporting the claim that this study relies on nuclear RNA rather than integrated cellular transcriptomic, epigenetic and proteomic profiling. But the ‘Changes in cell sub-populations’ and ‘Activated fibroblasts in DCM and HCM’ sections identify macrophage sub-populations and a disease-associated activated fibroblast population. The paper therefore does not support the implication that its approach cannot provide a granular picture of those populations, or establish that the additional profiling is necessary to do so. (LLM, conf=0.86)
- Disputedcites [20] Koenig, A. L. et al. Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure. Nat. Cardiovasc. Res. 1, 263–280 (2022). sourceExperimental — accuracy not yet measured
The Results section (‘snRNA-seq and scRNA-seq reveal the cellular landscape of the human heart’; page unavailable) says this study sequenced both nuclei and whole cells, contrary to the claim that it relied only on nuclear RNA and lacked cellular transcriptomic profiling. The Discussion (page unavailable) also describes distinct fibroblast populations in healthy and failing hearts. The paper does not establish the claim about missing epigenetic or proteomic profiling. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
- Disputedcites [21] Litviňuková, M. et al. Cells of the adult human heart. Nature 588, 466–472 (2020). sourceExperimental — accuracy not yet measured
The Main section (page unavailable) says this study combines snRNA-seq with scRNA-seq to enrich immune-cell populations; the Discussion likewise describes combined single-cell and single-nucleus data. Thus, contrary to the claim, this source does not rely only on nuclear RNA or lack cellular transcriptomic profiling. It studies the healthy adult heart rather than profiling immune and fibroblast populations emerging in heart failure. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
- Partly supportedcites [22] Reichart, D. et al. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science 377, eabo1984 (2022). sourceExperimental — accuracy not yet measured
The Abstract and Methods describe a study based on single-nucleus RNA sequencing, and the Discussion calls for future epigenomic and proteomic work. But the Results already distinguish fibroblast states and 14 myeloid subclusters and discuss fibroblast–macrophage interactions in fibrosis. The source therefore supports the missing-modality point, not the implication that its nuclear-RNA data cannot provide a granular picture of those populations. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“there are at present no approved treatments that directly target cardiac fibrosis3,4.”
§ Targeting immune–fibroblast cell communication in heart failure > Abstract
What the sources say
- Could not verifycites [3] Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022). sourceExperimental — accuracy not yet measured
The Abstract says trials of anti-fibrotic therapeutics have shown at most modest effects and that these interventions aim to limit progression rather than remodel established fibrosis. It does not state whether any treatment that directly targets cardiac fibrosis has been approved; searches for approved anti-fibrotic treatments found no passage resolving that point. (LLM, conf=0.72)
- Supportedcites [4] Aghajanian, H. et al. Targeting cardiac fibrosis with engineered T cells. Nature 573, 430–433 (2019). source
The Abstract states that no therapies are known to directly target excessive fibrosis. In the paper’s discussion of cardiac fibrosis, this supports the claim that no approved treatment directly targets it. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“To validate our findings, we used spatial transcriptomics data from human MI25 at days 2, 11, 62 and 153 post-MI and found FAP expression was most prominent acutely after MI and diminished at later time points (Fig. 2e, bottom).”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
What the sources say
- Supportedcites [25] Kuppe, C. et al. Spatial multi-omic map of human myocardial infarction. Nature https://doi.org/10.1038/s41586-022-05060-x (2022). source
The citation identifies the human MI spatial-transcriptomics dataset used by the citing authors. The source’s “Multi-omic map of myocardial infarction” section describes spatial transcriptomics of human heart tissue collected at different stages after MI. The FAP expression pattern is presented as the citing authors’ own finding, not a finding attributed to this source. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In support of this concept, a large clinical trial targeting the IL-1β pathway with the neutralizing antibody canakinumab led to a reduction in cardiac events31.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Supportedcites [31] Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017). source
The Methods describe a randomized trial of 10,061 patients using canakinumab, a monoclonal antibody targeting interleukin-1β. The Conclusions report significantly fewer recurrent cardiovascular events with the 150-mg dose than with placebo in patients with previous myocardial infarction and elevated C-reactive protein. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We chose to focus on IL-1β signalling given the availability and clinical efficacy of the anti-IL-1β monoclonal antibody (mAb) canakinumab31.”
§ Targeting immune–fibroblast cell communication in heart failure > Inflammatory signalling in fibrotic niches
What the sources say
- Supportedcites [31] Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017). source
The Methods identify canakinumab as a monoclonal antibody targeting IL-1β. The Conclusions report clinical efficacy: the 150-mg dose significantly lowered recurrent cardiovascular events versus placebo in patients with prior myocardial infarction and elevated C-reactive protein. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“and resemble POSTN-expressing matrifibrocytes7.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Partly supportedcites [7] Fu, X. et al. Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart. J. Clin. Invest. 128, 2127–2143 (2018). sourceExperimental — accuracy not yet measured
The Results section on cardiac fibroblast proliferation following MI reports Postn expression in activated cardiac fibroblasts, and the Discussion describes matrifibrocytes as a later fibroblast state in the scar (pages not provided). Our copy does not identify FAP-positive fibroblasts or compare them with matrifibrocytes, so the claimed resemblance is not established. (LLM, conf=0.79)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“By contrast, cultured human primary cardiac and dermal fibroblasts and immortalized cardiac fibroblasts were relatively poor models of human cardiac fibroblast diversity under resting or stimulated (TGFβ (refs. 19,39,40), IL-1β (ref. 41)) conditions.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Partly supportedcites [19] Chaffin, M. et al. Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy. Nature https://doi.org/10.1038/S41586-022-04817-8 (2022). sourceExperimental — accuracy not yet measured
The Cardiac fibrosis assay and Methods sections (pages unavailable) describe stimulating cultured human cardiac fibroblasts with TGFβ1, supporting the TGFβ condition cited in the sentence. The paper does not compare cultured cardiac, dermal, and immortalized fibroblasts as models of human cardiac fibroblast diversity. Its Discussion instead says it is not yet known how well the cultured-cell transition reflects the trajectory inferred from single-nucleus data. (LLM, conf=0.82)
- Supportedcites [39] Khalil, H. et al. Fibroblast-specific TGF-β–Smad2/3 signaling underlies cardiac fibrosis. J. Clin. Invest. 127, 3770–3783 (2017). source
The citation is attached to TGFβ as a stimulation condition, rather than to the citing authors’ assessment of model fidelity. The Methods (p. 11) describe treating cultured heart and skin fibroblasts with TGFβ, and the Results (p. 3) report responses of TGFβ-stimulated primary cardiac fibroblasts. (LLM, conf=0.89)
- Partly supportedcites [40] Stratton, M. S. et al. Dynamic chromatin targeting of BRD4 stimulates cardiac fibroblast activation. Circ. Res. 125, 662 (2019). sourceExperimental — accuracy not yet measured
The Results section, “BRD4 inhibition blocks TGF-β-mediated cardiac fibroblast activation” (page unavailable), documents TGF-β stimulation of cultured primary adult rat ventricular fibroblasts. The cited paper therefore supports the stimulation condition, but not its application to cultured human fibroblasts. The assessment that the cultures were poor models of human cardiac fibroblast diversity is the citing authors’ own conclusion, not a finding established by this source. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [41] Bujak, M. & Frangogiannis, N. G. The role of interleukin-1 in the pathogenesis of heart disease. Arch. Immunol. Ther. Exp. (Warsz.) 57, 165 (2009). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Consistent with our findings, the Srivastava laboratory has shown that Brd4 deletion in macrophages abrogates IL-1β signalling and suppresses fibroblast activation and fibrosis through a MEOX1-dependent regulatory mechanism in a pressure-overload model of HF30.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Partly supportedcites [30] Alexanian, M. et al. Chromatin remodelling drives immune–fibroblast crosstalk in heart failure pathogenesis. Nature https://doi.org/10.1038/s41586-024-08085-6 (2024). sourceExperimental — accuracy not yet measured
In “BRD4 function in Cx3cr1+ cells during heart failure,” Brd4 deletion in Cx3cr1-positive cells reduced fibrosis after pressure overload; “BRD4 in Cx3cr1+ cells activates fibroblasts” reports reduced profibrotic fibroblast programs. The paper also links IL1B to MEOX1-dependent fibroblast activation, but “BRD4 drives proinflammatory transcription” reports decreased Il1b expression after Brd4 deletion, not that IL-1β signalling was abrogated. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These findings are underscored by concurrent work establishing a role for MEOX1 in the pathogenesis of cardiac fibrosis30.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Supportedcites [30] Alexanian, M. et al. Chromatin remodelling drives immune–fibroblast crosstalk in heart failure pathogenesis. Nature https://doi.org/10.1038/s41586-024-08085-6 (2024). source
In “IL1B drives profibrotic function via MEOX1” (page not provided), the paper reports that MEOX1 knockdown abolished the increased contractility of stimulated cardiac fibroblasts. The Conclusion (page not provided) identifies MEOX1 as a critical regulator of the stress-activated fibroblast response in heart failure, supporting the attributed role in cardiac fibrosis. (LLM, conf=0.92)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We demonstrated that IL-1β was selectively expressed by CCR2+ monocytes and macrophages in the human heart, consistent with our earlier mouse studies42,43.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Partly supportedcites [42] Bajpai, G. et al. Tissue resident CCR2− and CCR2+ cardiac macrophages differentially orchestrate monocyte recruitment and fate specification following myocardial injury. Circ. Res. 124, 263–278 (2019). sourceExperimental — accuracy not yet measured
The Results section on monocyte-derived macrophages reports higher Il1β expression in recruited CCR2+ macrophages from injured mouse hearts. It does not establish selective expression by CCR2+ monocytes and macrophages in the human heart; the paper mentions human cardiac macrophage subsets but does not report this IL-1β finding in humans. No page numbers are available in our copy. (LLM, conf=0.84)
- Partly supportedcites [43] Bajpai, G. et al. The human heart contains distinct macrophage subsets with divergent origins and functions. Nat. Med. 24, 1234–1245 (2018). sourceExperimental — accuracy not yet measured
The paper reports that human cardiac CCR2+ macrophages expressed more IL-1β than CCR2− macrophages (section ‘CCR2+ macrophages represent an inflammatory population’; Fig. 5a–c). It also identifies CCR2+ monocytes in the heart, but the passages do not establish that those monocytes selectively expressed IL-1β. (LLM, conf=0.87)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- Probably not a substantial claim. 22
- It may state two separate claims as one. 39
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, previous and concurrent work has highlighted the functional role of this gene regulatory network in cardiac fibrosis28–30.”
§ Targeting immune–fibroblast cell communication in heart failure > Cardiac fibroblast lineage specification
What the sources say
- Supportedcites [28] Alexanian, M. et al. A transcriptional switch governs fibroblast activation in heart disease. Nature 595, 438–443 (2021). source
In “MEOX1 regulates pro-fibrotic function” (page unavailable), Meox1 depletion reduced functional hallmarks of myofibroblast activation and transcription of fibrotic-program genes. This supports citing the paper as work highlighting a functional role for the regulatory network in cardiac fibrosis. (LLM, conf=0.90)
- Partly supportedcites [29] Amrute, J. M. et al. Defining cardiac functional recovery in end-stage heart failure at single-cell resolution. Nat. Cardiovasc. Res. 2, 399–416 (2023). sourceExperimental — accuracy not yet measured
In Results (‘RUNX1 GRN is associated with recovery’; page unavailable), the paper reports that simulated RUNX1 deletion shifts fibroblasts away from states associated with fibrosis and heart failure. This supports a proposed role for the network, but the perturbation was in silico; the paper does not establish a functional role in cardiac fibrosis experimentally. (LLM, conf=0.84)
- Supportedcites [30] Alexanian, M. et al. Chromatin remodelling drives immune–fibroblast crosstalk in heart failure pathogenesis. Nature https://doi.org/10.1038/s41586-024-08085-6 (2024). source
The Conclusion identifies a BRD4–IL1B–MEOX1 regulatory pathway that drives fibroblast activation and fibrosis. In “IL1B inhibition improves heart function,” blocking IL1B reduced fibrosis in mice, providing functional evidence for the pathway’s role in cardiac fibrosis. The supplied passages do not give page numbers. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“cardiac fibrosis is prominent in patients who suffer a myocardial infarction (MI) and in those with ischaemic and non-ischaemic cardiomyopathies (ICM and NICM)5,6.”
§ Targeting immune–fibroblast cell communication in heart failure > Abstract
What the sources say
- Not checked — no full text of the sourcecites [5] Gutstein, D. E. & Fuster, V. Pathophysiology and clinical significance of atherosclerotic plaque rupture. Cardiovasc. Res. 41, 323–333 (1999). source
- Partly supportedcites [6] Thygesen, K. et al. Third universal definition of myocardial infarction. Circulation 126, 2020–2035 (2012). sourceExperimental — accuracy not yet measured
The imaging discussion says that ischaemia and infarction can lead to healing by fibrosis, supporting the MI portion of the claim. The passages on heart failure and cardiomyopathy do not say that fibrosis is prominent in ischaemic or non-ischaemic cardiomyopathies, and the paper does not establish how prominent fibrosis is among MI patients. Page numbers were not available in our copy. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“we previously showed expansion of RUNX1-expressing cells in human HF29.”
§ Targeting immune–fibroblast cell communication in heart failure > Cardiac fibroblast lineage specification
What the sources say
- Supportedcites [29] Amrute, J. M. et al. Defining cardiac functional recovery in end-stage heart failure at single-cell resolution. Nat. Cardiovasc. Res. 2, 399–416 (2023). source
In Results (‘RUNX1 GRN is associated with recovery’), the authors report greater numbers of RUNX1-positive stromal cells in human pre-LVAD heart-failure samples than in donor samples. This supports the cited claim of expansion, specifically in the stromal-cell population measured. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Numerous single-nucleus RNA sequencing (snRNA-seq) studies have investigated the healthy and failing human heart18–22.”
§ Targeting immune–fibroblast cell communication in heart failure > Abstract
What the sources say
- Not checked — no full text of the sourcecites [18] Tucker, N. R. et al. Transcriptional and cellular diversity of the human heart. Circulation 142, 466–482 (2020). source
- Supportedcites [19] Chaffin, M. et al. Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy. Nature https://doi.org/10.1038/S41586-022-04817-8 (2022). source
The Expression profiles of cardiomyopathies section reports an snRNA-seq study of human left ventricles from non-failing hearts and patients with advanced cardiomyopathy. This paper therefore exemplifies the type of study described in the citing sentence; the citation need not establish the number of such studies on its own. (LLM, conf=0.93)
- Supportedcites [20] Koenig, A. L. et al. Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure. Nat. Cardiovasc. Res. 1, 263–280 (2022). source
The Results section (‘snRNA-seq and scRNA-seq reveal the cellular landscape of the human heart’) describes this paper’s single-nucleus RNA sequencing of non-diseased and failing human hearts. It therefore supports its use as one example among the studies cited; the claim does not require this paper alone to establish that there were numerous studies. (LLM, conf=0.93)
- Supportedcites [21] Litviňuková, M. et al. Cells of the adult human heart. Nature 588, 466–472 (2020). source
The Main section says the study incorporates snRNA-seq and defines cellular and molecular signatures of the adult healthy heart. It therefore serves as an example of the studies cited collectively; the sentence does not require each cited study to investigate both healthy and failing hearts. (LLM, conf=0.89)
- Supportedcites [22] Reichart, D. et al. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science 377, eabo1984 (2022). source
The Abstract describes an snRNA-seq study of 18 control and 61 failing human hearts. This paper is therefore an example of the studies cited in the sentence; it need not establish the total number of studies. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
Every source the paper cites for this claim was checked and supports it.
In the paper
“MEOX1 was previously implicated in cardiac fibrosis28.”
§ Targeting immune–fibroblast cell communication in heart failure > Cardiac fibroblast lineage specification
What the sources say
- Supportedcites [28] Alexanian, M. et al. A transcriptional switch governs fibroblast activation in heart disease. Nature 595, 438–443 (2021). source
The paper’s “MEOX1 regulates pro-fibrotic function” section identifies MEOX1 as a mediator of the fibroblast-to-myofibroblast switch associated with fibrotic disease. Its “MEOX1 is upregulated in human fibrosis” section also reports MEOX1 expression in activated cardiac fibroblasts and increased expression in heart tissue from patients with cardiomyopathy. The supplied passages have no page numbers. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Recent studies have implicated a potential pathogenic role for FAP+ fibroblasts in mouse models of cardiac remodelling3,4.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Supportedcites [3] Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022). source
The Abstract reports that eliminating activated fibroblasts in a mouse model of heart disease reduced cardiac fibrosis and improved function. It also reports improved function in injured mice treated with FAP-targeting CAR T cells, supporting a potential pathogenic role for FAP-positive fibroblasts in cardiac remodelling. (LLM, conf=0.92)
- Supportedcites [4] Aghajanian, H. et al. Targeting cardiac fibrosis with engineered T cells. Nature 573, 430–433 (2019). source
The paper reports Fap expression on activated cardiac fibroblasts in mouse models of cardiac injury (Fig. 2c; Extended Data Fig. 3). It also reports that targeting those cells with FAP CAR T cells reduced fibrosis and partially rescued cardiac function in injured mice (Fig. 3), supporting a potential pathogenic role. (LLM, conf=0.93)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“They also show that anti-IL-1β mAb treatment leads to fewer POSTN fibroblasts, improved cardiac function and decreased cardiac fibrosis30.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Partly supportedcites [30] Alexanian, M. et al. Chromatin remodelling drives immune–fibroblast crosstalk in heart failure pathogenesis. Nature https://doi.org/10.1038/s41586-024-08085-6 (2024). sourceExperimental — accuracy not yet measured
The section ‘IL1B inhibition improves heart function’ reports that anti-IL1B treatment in mice reduced the representation of Postn-enriched fibroblast clusters, improved cardiac function and reduced fibrosis. The Methods identify the treatment as an anti-IL1B antibody but do not specify that it was monoclonal, so the ‘mAb’ detail is not established by our copy. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Consistent with these findings, concurrent work showed that anti-IL-1β mAb treatment improved cardiac function and reduced fibrosis in a TAC HF model30.”
§ Targeting immune–fibroblast cell communication in heart failure > IL-1β drives fibroblast activation
What the sources say
- Supportedcites [30] Alexanian, M. et al. Chromatin remodelling drives immune–fibroblast crosstalk in heart failure pathogenesis. Nature https://doi.org/10.1038/s41586-024-08085-6 (2024). source
The section “IL1B inhibition improves heart function” reports that mice subjected to TAC and treated with IL1B-neutralizing antibodies had significantly improved cardiac function and reduced fibrosis compared with IgG-treated controls. The Methods section confirms the antibody treatment in the TAC model. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The possibility that JQ1 treatment can reversibly direct fibroblast activation away from the FAP/POSTN cell state indicates the therapeutic potential of targeting the differentiation and maturation of FAP+ fibroblasts28,30.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
What the sources say
- Partly supportedcites [28] Alexanian, M. et al. A transcriptional switch governs fibroblast activation in heart disease. Nature 595, 438–443 (2021). sourceExperimental — accuracy not yet measured
In “Transcriptional plasticity of fibroblasts” (page unavailable), the paper reports that JQ1 shifted stressed cardiac fibroblasts toward a sham-like state and reduced Postn expression; withdrawal reversed these effects. Our copy does not identify a FAP/POSTN cell state or specifically establish that JQ1 targets the differentiation and maturation of FAP-positive fibroblasts. (LLM, conf=0.84)
- Partly supportedcites [30] Alexanian, M. et al. Chromatin remodelling drives immune–fibroblast crosstalk in heart failure pathogenesis. Nature https://doi.org/10.1038/s41586-024-08085-6 (2024). sourceExperimental — accuracy not yet measured
In “BRD4 in Cx3cr1+ cells activates fibroblasts” (page unavailable), the paper reports that JQ1 downregulated fibroblast genes including the profibrotic marker Postn. Its introduction describes a reversible fibroblast-activation switch under BET inhibition, but the paper does not establish that JQ1 reversibly redirects a FAP/POSTN-defined cell state or specifically targets the differentiation and maturation of FAP-positive fibroblasts. (LLM, conf=0.84)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“We first mapped the mouse MI dataset onto the global human CITE-seq reference and detected strong mapping across all populations with early immune expansion and transcriptional shifts in fibroblasts (Supplementary Fig. 3a–e).”
§ Targeting immune–fibroblast cell communication in heart failure > Experimental models of cardiac fibrosis
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In the paper
“Consistent with mouse MI and TAC models, we saw expansion of F9 after injury and we found strong mapping scores for most fibroblast populations except for F5 and F6 (Fig. 3c–e and Supplementary Table 17).”
§ Targeting immune–fibroblast cell communication in heart failure > Experimental models of cardiac fibrosis
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“F9 fibroblasts were strongly enriched for FAP at the RNA and cell surface protein levels and co-expressed POSTN (Fig. 2c).”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
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In the paper
“F9 fibroblasts were most similar to cancer-associated fibroblasts and F4 fibroblasts mapped to idiopathic pulmonary fibrosis fibroblasts (Fig. 2g).”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We observed expansion of myeloid and T cells following AMI with the greatest expansion in myeloid cells occurring within the first week (Fig. 1e and Extended Data Fig. 1e).”
§ Targeting immune–fibroblast cell communication in heart failure > Multiomic map of human heart failure
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In the paper
“We performed in vivo lineage tracing of fibroblast activator protein (FAP) fibroblasts to show that they selectively contribute to a lineage of periostin (POSTN)-expressing fibroblasts that is distinct from myofibroblasts.”
- Also stated in: § Cardiac fibroblast lineage specification · plain
“Quantification of tdTomato+Postn+ and tdTomato+ACTA2+ cells showed that Fap+ cells contributed towards the POSTN lineage but not the ACTA2 myofibroblast lineage (Fig. 2n).”
§ Targeting immune–fibroblast cell communication in heart failure > Abstract
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- Also stated in: § Cardiac fibroblast lineage specification · plain
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In the paper
“None of these genes correlated with ACTA2 expression or were evident within the myofibroblast trajectory or state (F2) (Fig. 2p and Extended Data Fig. 4b).”
§ Targeting immune–fibroblast cell communication in heart failure > Cardiac fibroblast lineage specification
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In the paper
“Following JQ1 withdrawal, F9 fibroblasts re-emerge, suggesting that this is a reversible effect (Extended Data Fig. 6d).”
§ Targeting immune–fibroblast cell communication in heart failure > Experimental models of cardiac fibrosis
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In the paper
“We reference mapped the fibroblast populations from human coronaries to our human cardiac fibroblasts and found that F2 and F11 fibroblasts displayed the greatest mapping to the coronary adventitia. F9 fibroblasts were absent from perivascular areas (Fig. 2h).”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
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In the paper
“The donor fibroblast signature was most enriched early in pseudotime, whereas the diseased signature increased with pseudotime along each trajectory (Extended Data Fig. 5b, top).”
§ Targeting immune–fibroblast cell communication in heart failure > Cardiac fibroblast lineage specification
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In the paper
“The FAP/POSTN transcriptional signature peaked early after MI, declined over a 3 month period and remained chronically elevated thereafter (Fig. 2e, top).”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
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In the paper
“An integrated analysis across seven ischaemic samples (Extended Data Fig. 4g) suggested that most fibroblast cell states displayed independent localizations. Only F6–F11 and F12–F13 displayed strong co-localization.”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
hedgedcorrelationaln = 7- Asserted: passes — The authors put it forward as true.
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In the paper
“This analysis showed that F2 fibroblasts are associated with perivascular cells (pericytes) whereas F9 fibroblasts are associated with myeloid cells and F4 fibroblasts (Extended Data Fig. 4h).”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
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In the paper
“Analysis across time points following MI revealed marked expansion of F9 fibroblasts that peaked on day 7 post-MI and remained elevated compared with sham on day 28 post-MI (Fig. 3b and Extended Data Fig. 6b).”
§ Targeting immune–fibroblast cell communication in heart failure > Experimental models of cardiac fibrosis
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We next performed pseudobulk DEG analysis between donor and diseased fibroblasts and found that the diseased signature gene mapped to F9 fibroblasts, whereas the donor signature localized within F5, F7 and F11 fibroblasts (Extended Data Fig. 4a,b).”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
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In the paper
“Immunostaining for FAP in left-ventricle sections showed minimal expression in donors, intermediate expression in chronic ICM and NICM, and robust expression following AMI (Fig. 2d).”
§ Targeting immune–fibroblast cell communication in heart failure > Fibroblast cell states in HF
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Notably, F9 fibroblasts had the greatest number of intersecting genes and displayed marked enrichment of this gene set relative to other fibroblast states including myofibroblasts (F2) (Fig. 2r).”
§ Targeting immune–fibroblast cell communication in heart failure > Cardiac fibroblast lineage specification
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In the paper
“Significantly different cell distributions between the FAP+ and FAP− groups were observed with enrichment of Postn/Cthrc1 cells in the FAP+ fibroblast group (Extended Data Fig. 10i).”
§ Targeting immune–fibroblast cell communication in heart failure > IL-1β drives fibroblast activation
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that although there was minimal variability among technical replicates, there was some biological variability across batches, highlighting baseline plasticity inherent in cultured fibroblast preparations (Extended Data Fig. 7a–c and Supplementary Table 18).”
§ Targeting immune–fibroblast cell communication in heart failure > Experimental models of cardiac fibrosis
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In the paper
“Both mouse models displayed reduced FAP+ fibroblasts, diminished fibrosis and improved cardiac function.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
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In the paper
“CCR2+ macrophages co-localized with F9 fibroblasts whereas resident macrophages co-localized with F4 fibroblasts (Fig. 4f and Supplementary Table 23).”
§ Targeting immune–fibroblast cell communication in heart failure > Inflammatory signalling in fibrotic niches
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“TGFβ treatment led to a modest expansion in F9 fibroblasts in the PHCF and PHDF models; however, these cells displayed suboptimal mapping to the human CITE-seq dataset (Fig. 3g and Supplementary Table 19).”
§ Targeting immune–fibroblast cell communication in heart failure > Experimental models of cardiac fibrosis
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-1β was specifically expressed in myeloid cells (Fig. 4b) and more specifically within CCR2+ monocytes and macrophages and classic dendritic cells (DC2s) (Fig. 4b,c, Extended Data Fig. 8a–f and Supplementary Table 20), each of which co-localized in the infarct region using spatial transcriptomics data (Fig. 4c and Extended Data Fig. 8g,h).”
§ Targeting immune–fibroblast cell communication in heart failure > Inflammatory signalling in fibrotic niches
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Notably, F2 fibroblasts co-localized with SMCs, pericytes and endothelium and did not co-localize with CCR2+ macrophages (Fig. 4f).”
§ Targeting immune–fibroblast cell communication in heart failure > Inflammatory signalling in fibrotic niches
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“These findings establish a direct and clinically significant role for inflammation in fibroblast lineage specification and tissue fibrosis.”
§ Targeting immune–fibroblast cell communication in heart failure > Abstract
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In the paper
“Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction1,2.”
§ Targeting immune–fibroblast cell communication in heart failure > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Multiple biological and technical replicates were included, individually hash tagged and pooled to minimize any potential batch effects (Fig. 3f and Supplementary Fig. 4).”
§ Targeting immune–fibroblast cell communication in heart failure > Experimental models of cardiac fibrosis
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These findings reflect the complexity of cardiac fibrosis driven by signals from multiple cardiac cell types and emphasize the relevance of in vivo mouse models in studying cardiac fibrosis and for therapeutic discovery.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
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In the paper
“For human studies, all transplants with HF, MI and non-failing donors were processed, randomized across age, sex and race.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Statistics and reproducibility
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In the paper
“Informed consent was obtained from each patient before tissue collection by Washington University School of Medicine and no compensation was provided in exchange for subject participation in the study.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Ethical approval for human specimens
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In the paper
“Investigators were blinded to the groups when performing initial analyses.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Statistics and reproducibility
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In the paper
“Patients included in this study span diverse race, age and sex to provide an inclusive trans-ethnic study population.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Ethical approval for human specimens
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In the paper
“The study is compliant with all relevant ethical regulations and has been approved by the Washington University School of Medicine Institutional Review Board (IRB no. 201104172).”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Ethical approval for human specimens
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In the paper
“cells passing the following criteria were kept for downstream processing: 500 < nFeature_RNA < 600 and 1,000 < nCount_RNA < 25,000 and percentage mitochondrial reads less than 15%.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > CITE-seq alignment, quality control and cell type annotation
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and acknowledge that further studies are necessary to understand the applicability of our results to other cardiac pathologies.”
§ Targeting immune–fibroblast cell communication in heart failure > Discussion
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Quality control was performed to keep nuclei with the following: TSS enrichment > 2, nFrags > 1,000, 200 < nUMI GEX < 50,000 and percent mito < 5%.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Multiome data processing
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Probably not a substantial claim. It may state two separate claims as one.
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In the paper
“All single-cell/-nucleus analyses including clustering were done using unbiased techniques.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Statistics and reproducibility
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In vivo experiments were replicated at least once for a total of two batches and data were pooled for downstream analysis (all attempts at replication were successful).”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Statistics and reproducibility
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For in vivo studies, male and female mice were used and randomized to sham and treatment groups, and littermate controls were used in genetic studies.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Statistics and reproducibility
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Blinding during data collection was not necessary as the nuclei isolation protocol required FACS to collect intact cells/nuclei with no exclusion of any cells/nuclei. This sorting approach does not introduce any bias into the sample collection.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Statistics and reproducibility
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Individuals were partially blinded to the sample groups.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Animal experiments
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No sample size calculations were performed.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Animal experiments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Any patients with human immunodeficiency virus or hepatitis or known genetic cardiomyopathies were excluded from this study.”
§ Targeting immune–fibroblast cell communication in heart failure > Methods > Inclusion criteria
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The molecular mechanisms driving immune–fibroblast communication in human cardiac disease remain unexplored.
“However, the molecular mechanisms driving immune–fibroblast cell communication in human cardiac disease remain unexplored and there are at present no approved treatments that directly target cardiac fibrosis3,4.”
The paper relies on this without support.
Strategies to therapeutically target cardiac fibrosis have remained elusive.
“Strategies to therapeutically target cardiac fibrosis have remained elusive.”
The paper relies on this without support.
The precise fibroblast populations responsible for fibrosis in the human heart and the mechanisms orchestrating their emergence and maturation are unknown.
“However, the precise fibroblast populations that are responsible for fibrosis in the human heart and mechanisms that orchestrate their emergence and maturation are unknown.”
The paper relies on this without support.
It is not clear which preclinical in vitro and in vivo models best recapitulate human cardiac fibroblast subtypes.
“Furthermore, it is not clear which of the many available preclinical in vitro and in vivo models10–15 best recapitulate human cardiac fibroblast subtypes.”
The paper relies on this without support.
No large-scale study to date performs single-cell or epitope-based sequencing in human hearts.
“Given the many challenges associated with collecting fresh cardiac left-ventricle tissue, there is no large-scale study to date that performs single-cell or epitope-based sequencing in human hearts.”
The paper relies on this without support.
Little is known about the mechanisms and signalling events that orchestrate the specification of pathogenic fibroblasts in human myocardial infarction and heart failure.
“Little is known regarding the mechanisms and signalling events that orchestrate the specification of pathogenic fibroblasts in the context of human MI and HF.”
The paper relies on this without support.
Little is understood about the signalling mechanisms that underlie the specification and differentiation of pathological fibroblasts in the heart.
“Little is understood regarding the signalling mechanisms that underlie the specification and differentiation of pathological fibroblasts in the heart.”
The paper relies on this without support.
The potential for inflammatory signals to drive fibroblast activation and cardiac fibrosis is less explored.
“the potential for inflammatory signals to drive fibroblast activation and cardiac fibrosis is less explored.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“a parallel contemporaneous study utilizing explanted human heart tissue from patients with cardiomyopathy or acute myocardial infarction independently identified IL1B-mediated macrophage-fibroblast communication as a regulator of pathologic fibroblast activation35.”
From Chromatin remodelling drives immune cell–fibroblast communication in heart failure (2024) · cites this paper as [35]
Citations
Cites
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Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
Third universal definition of myocardial infarction
the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Thygesen, K., Alpert, J. S., Jaffe, A. S., Simoons, M. L., CHAITMAN, B. R., & White, H. D. (2012) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2012.122 · Cited by 6,585
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Simultaneous epitope and transcriptome measurement in single cells
Stoeckius, M., Hafemeister, C., Stephenson, W., Houck-Loomis, B., Chattopadhyay, P. K., Swerdlow, H., Satija, R., & Smibert, P. (2017) · Nature Methods · doi:10.1038/nmeth.4380 · Cited by 3,098
Cited by
Sorted by citations
Chromatin remodelling drives immune cell–fibroblast communication in heart failure
Alexanian, M., Padmanabhan, A., Nishino, T., Travers, J. G., Ye, L., Pelonero, A., Lee, C. Y., Sadagopan, N., Huang, Y., Auclair, K., et al. (2024) · Nature · doi:10.1038/s41586-024-08085-6 · Cited by 140
Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure
Ghazal, R., Wang, M., Liu, D., Tschumperlin, D. J., & Pereira, N. L. (2025) · Circulation Research · doi:10.1161/circresaha.124.325402 · Cited by 128
Selective inhibition of stromal mechanosensing suppresses cardiac fibrosis
Cho, S., Rhee, S., Madl, C. M., Caudal, A., Thomas, D., Kim, H., Kojic, A., Shin, H. S., Mahajan, A., Jahng, J. W. S., et al. (2025) · Nature · doi:10.1038/s41586-025-08945-9 · Cited by 75
Immunometabolism in heart failure
Andreadou, I., Ghigo, A., Nikolaou, P., Świrski, F. K., Thackeray, J. T., Heusch, G., & Vilahur, G. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01165-8 · Cited by 76
Functional diversity of cardiac macrophages in health and disease
Yang, S. H., Penna, V. R., & Lavine, K. J. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01109-8 · Cited by 67
Self-citation
Metadata
- Authors
- Amrute, J. M., Luo, X., Penna, V., Yang, S., Yamawaki, T., Hayat, S., Bredemeyer, A., Jung, I.-H., Kadyrov, F. F., Heo, G. S., Venkatesan, R., Shi, S. Y., Parvathaneni, A., Koenig, A. L., Kuppe, C., Baker, C., Luehmann, H., Jones, C., Kopecky, B., Zeng, X., Bleckwehl, T., Ma, P., Lee, P., Terada, Y., Fu, A., Furtado, M., Kreisel, D., Kovacs, A., Stitziel, N. O., Jackson, S., Li, C.-M., Liu, Y., Rosenthal, N. A., Kramann, R., Ason, B., & Lavine, K. J.
- Affiliations
- Washington University in St. Louis (US)
- Amgen (United States) (US)
- RWTH Aachen University (DE)
- Jackson Laboratory (US)
- Erasmus MC (NL)
- Corresponding author
- Lavine, Kory J.
- ORCID
- Amrute, Junedh M.
- Luo, Xin
- Penna, Vinay
- Yang, Steven
- Yamawaki, Tracy
- Hayat, Sikander
- Bredemeyer, Andrea
- Jung, In-Hyuk
- Kadyrov, Farid F.
- Heo, Gyu Seong
- Venkatesan, Rajiu
- Shi, Sally Yu
- Parvathaneni, Alekhya
- Koenig, Andrew L.
- Kuppe, Christoph
- Baker, Candice
- Luehmann, Hannah
- Jones, Cameran
- Kopecky, Benjamin
- Zeng, Xue
- Bleckwehl, Tore
- Ma, Pan
- Lee, Paul
- Terada, Yuriko
- Furtado, Milena
- Kreisel, Daniel
- Stitziel, Nathan O.
- Li, Chi-Ming
- Liu, Yongjian
- Rosenthal, Nadia A.
- Kramann, Rafael
- Lavine, Kory J.
- Venue
- Nature
- Published
- 2024-10-23
- Volume
- 635
- Issue
- 8038
- Pages
- 423-433
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC12334188
- OpenAlex
- W4403680192
- Semantic Scholar
- 5098d84a7bc4ba425abd3ade8ebc0c7433e07a6c
- Cited by
- 339
- References
- 55
- Citations by year
- 2026: 188 · 2025: 127 · 2024: 17
- FWCI
- 92.76
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- Research Square (submittedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Funders
- American Heart Association (916955, 826325)
- Washington University in St. Louis
- Children's Discovery Institute (PM-LI-2019-829, CH-II-2015-462)
- Alvin J. Siteman Cancer Center (CA91842, #P30 CA91842)
- Fondation Leducq (20CVD02)
- National Institutes of Health (1s10od028597-01)
- National Heart, Lung, and Blood Institute (R01HL138466, R01HL151078, R01HL139714, R35HL161185, R35HL145212)
- National Cancer Institute (P30CA091842)
- National Institute of General Medical Sciences (T32GM007200)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR073752)
- National Institute of Biomedical Imaging and Bioengineering (P41EB025815)
- National Center for Research Resources
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- heart failure, myocardial fibrosis, myofibroblasts, cancer-associated fibroblasts, CCR2+ macrophages, inflammation, periostin, ETA receptor, transcription factor perturbation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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