The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF
Abstract
Rationale: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF. Objective: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model. Methods and Results: By combining the age, long-term high-fat diet, and desoxycorticosterone pivalate challenge in a mouse model, we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of IL (interleukin)-1β/IL-18 and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing β-hydroxybutyrate level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokine–triggered mitochondrial dysfunction and fibrosis. Moreover, β-hydroxybutyrate downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of CS (citrate synthase) and inhibition of fatty acid uptake. Conclusions: Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis, which can be ameliorated by promoting β-hydroxybutyrate abundance.
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
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315
Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
Wiviott, S. D., Raz, I., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Silverman, M. G., Zelniker, T. A., Kuder, J. F., Murphy, S. A., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812389 · Cited by 6,382
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease
Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3804 · Cited by 2,172
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., et al. (2013) · Science · doi:10.1126/science.1227166 · Cited by 1,777
Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics
Puchalska, P., & Crawford, P. A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.022 · Cited by 1,610
Epidemiology of heart failure with preserved ejection fraction
Dunlay, S. M., Roger, V. L., & Redfield, M. M. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.65 · Cited by 1,534
Cahill, G. F. (2006) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.26.061505.111258 · Cited by 1,319
Functions and mechanisms of non-histone protein acetylation
Narita, T., Weinert, B. T., & Choudhary, C. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0081-3 · Cited by 1,232
Hormone-fuel interrelationships during fasting.
Cahill, G. F., Herrera, M. G., Morgan, A. P., Soeldner, J. S., Steinke, J., Levy, P. L., Reichard, G. A., & Kipnis, D. M. (1966) · Journal of Clinical Investigation · doi:10.1172/jci105481 · Cited by 1,036
Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap
Shah, S. J., Kitzman, D. W., Borlaug, B. A., van Heerebeek, L., Zile, M. R., Kass, D. A., & Paulus, W. J. (2016) · Circulation · doi:10.1161/circulationaha.116.021884 · Cited by 1,003
Cited by
Cardiac Energy Metabolism in Heart Failure
Lopaschuk, G. D., Karwi, Q. G., Tian, R., Wende, A. R., & Abel, E. D. (2021) · Circulation Research · doi:10.1161/circresaha.121.318241 · Cited by 1,373
Self-citationEmpagliflozin in acute myocardial infarction: the EMMY trial
von Lewinski, D., Kolesnik, E., Tripolt, N. J., Pferschy, P. N., Benedikt, M., Wallner, M., Alber, H., Berger, R., Lichtenauer, M., Saely, C. H., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac494 · Cited by 303
“Hypertension, n (%) 199 (42) 92 (39) 107 (45) 0.”
Withaar, C., Lam, C. S. P., Schiattarella, G. G., de Boer, R. A., & Meems, L. M. G. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab389 · Cited by 150
Obesity accelerates cardiovascular ageing
Ruperez, C., Madeo, F., de Cabo, R., Kroemer, G., & Abdellatif, M. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf216 · Cited by 73
Cardiovascular disease and the biology of aging
Moturi, S., Ghosh-Choudhary, S. K., & Finkel, T. (2022) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2022.04.005 · Cited by 56
Metadata
- Authors
- Deng, Y., Xie, M., Li, Q., Xu, X., Ou, W., Zhang, Y., Xiao, H., Yu, H., Zheng, Y., Liang, Y., Jiang, C., Chen, G., Du, D., Zheng, W., Wang, S., Gong, M., Chen, Y., Tian, R., & Li, T.
- Venue
- Circulation Research
- Published
- 2021-01-22
- Volume
- 128
- Issue
- 2
- Pages
- 232-245
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W3101357080
- Cited by
- 409
- References
- 40
- FWCI
- 12.65
- 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: Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF. https://app.cochat.ai/papers/10.1161/circresaha.120.317933
- The paper
- Deng, Y., Xie, M., Li, Q., Xu, X., Ou, W., Zhang, Y., Xiao, H., Yu, H., Zheng, Y., Liang, Y., Jiang, C., Chen, G., Du, D., Zheng, W., Wang, S., Gong, M., Chen, Y., Tian, R., & Li, T. (2021). Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF. Circulation Research. https://doi.org/10.1161/circresaha.120.317933
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.
