The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult
Abstract
Aims: Rapid over-activation of β-adrenergic receptor (β-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute β-AR stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon β-AR insult. Methods and results: Male C57BL/6 mice were injected with a single dose of β-AR agonist, isoproterenol (ISO, 5 mg/kg body weight) or saline subcutaneously. Cytokine array profiling demonstrated that chemokines dominated the initial cytokines upregulation specifically within the heart upon β-AR insult, which promoted early macrophage infiltration. Further investigation revealed that the rapid inflammasome-dependent activation of IL-18, but not IL-1β, was the critical up-stream regulator for elevated chemokine expression in the myocardium upon ISO induced β1-AR-ROS signalling. Indeed, a positive correlation was observed between the serum levels of norepinephrine and IL-18 in patients with chest pain. Genetic deletion of IL-18 or the up-stream inflammasome component NLRP3 significantly attenuated ISO-induced chemokine expression and macrophage infiltration. In addition, IL-18 neutralizing antibodies selectively abated ISO-induced chemokines, proinflammatory cytokines and adhesion molecules but not growth factors. Moreover, blocking IL-18 early after ISO treatment effectively attenuated cardiac inflammation and fibrosis. Conclusion: Inflammasome-dependent activation of IL-18 within the myocardium upon acute β-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of β-AR insult can successfully prevent inflammatory responses and cardiac injuries.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Roffi, M., Patrono, C., Collet, J.-P., Mueller, C., Valgimigli, M., Andreotti, F., Bax, J. J., Borger, M. A., Brotons, C., Chew, D. P., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv320 · Cited by 8,261
The interleukin-1 family: back to the future
Garlanda, C., Dinarello, C. A., & Mantovani, A. (2013) · Immunity · doi:10.1016/j.immuni.2013.11.010 · Cited by 1,945 · cited 1×
“We next examined IL-1b and IL-18, both are known to enhance expression of chemokines and adhesion molecules.(9) Pro-IL-1b and pro-IL-18 need to be converted to the mature and active form by inflammasomedependent cleavage.”
BackgroundCardiac fibroblasts: At the heart of myocardial remodeling
Porter, K. E., & Turner, N. A. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.05.002 · Cited by 1,010
Inflammasomes and Their Roles in Health and Disease
Lamkanfi, M., & Dixit, V. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155745 · Cited by 935 · cited 1×
“Pro-IL-1b and pro-IL-18 need to be converted to the mature and active form by inflammasomedependent cleavage.(10) As shown in Figure 2A, ELISA assay detected a significant increase of active IL-18 at 1, 24, and 72 h in the heart after ISO treatment.”
BackgroundRedox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector?
Abais, J. M., Xia, M., Zhang, Y., Boini, K. M., & Li, P.-L. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2014.5994 · Cited by 928
Self-citationKawaguchi, M., Takahashi, M., Hata, T., Kashima, Y., Usui, F., Morimoto, H., Izawa, A., Takahashi, Y., Masumoto, J., Koyama, J., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.982777 · Cited by 884
Mezzaroma, E., Toldo, S., Farkas, D., Seropian, I. M., Van Tassell, B. W., Salloum, F. N., Kannan, H. R., Menna, A. C., Voelkel, N. F., & Abbate, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108586108 · Cited by 629
Sympathetic Overstimulation During Critical Illness: Adverse Effects of Adrenergic Stress
Dünser, M. W., & Hasibeder, W. R. (2009) · Journal of Intensive Care Medicine · doi:10.1177/0885066609340519 · Cited by 488
Cardiovascular reactivity, stress, and physical activity
Huang, C.-J., Webb, H. E., Zourdos, M. C., & Acevedo, E. O. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00314 · Cited by 305
Mechanisms of stress (Takotsubo) cardiomyopathy
Nef, H. M., Möllmann, H., Akashi, Y. J., & Hamm, C. W. (2010) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2010.16 · Cited by 264
Cited by
Frangogiannis, N. G. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa324 · Cited by 1,229
The NLRP3 inflammasome in acute myocardial infarction
Toldo, S., & Abbate, A. (2018) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.161 · Cited by 665
Inflammation and fibrosis in murine models of heart failure
Bacmeister, L., Schwarzl, M., Warnke, S., Stoffers, B., Blankenberg, S., Westermann, D., & Lindner, D. (2019) · Basic Research in Cardiology · doi:10.1007/s00395-019-0722-5 · Cited by 382
Macrophage and Fibroblast Interactions in Biomaterial‐Mediated Fibrosis
Witherel, C. E., Abebayehu, D., Barker, T. H., & Spiller, K. L. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201801451 · Cited by 374
Targeting the NLRP3 inflammasome in cardiovascular diseases
Toldo, S., Mezzaroma, E., Buckley, L. F., Potere, N., Di Nisio, M., Biondi-Zoccai, G., Van Tassell, B. W., & Abbate, A. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108053 · Cited by 328
Metadata
- Authors
- Xiao, H., Li, H., Wang, J.-J., Zhang, J.-S., Shen, J., An, X.-B., Zhang, C.-C., Wu, J.-M., Song, Y., Wang, X.-Y., Yu, H.-Y., Deng, X.-N., Li, Z.-J., Xu, M., Lu, Z.-Z., Du, J., Gao, W., Zhang, A.-H., Feng, Y., & Zhang, Y.-Y.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-05-26
- Volume
- 39
- Issue
- 1
- Pages
- 60-69
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2617615685
- Cited by
- 305
- References
- 19
- FWCI
- 15.04
- Type
- journal article
- Language
- en
- Open access
- closed
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult. https://app.cochat.ai/papers/10.1093/eurheartj/ehx261
- The paper
- Xiao, H., Li, H., Wang, J.-J., Zhang, J.-S., Shen, J., An, X.-B., Zhang, C.-C., Wu, J.-M., Song, Y., Wang, X.-Y., Yu, H.-Y., Deng, X.-N., Li, Z.-J., Xu, M., Lu, Z.-Z., Du, J., Gao, W., Zhang, A.-H., Feng, Y., & Zhang, Y.-Y. (2018). IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult. European Heart Journal. https://doi.org/10.1093/eurheartj/ehx261
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
