The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.
Empagliflozin Blunts Worsening Cardiac Dysfunction Associated With Reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) Inflammasome Activation in Heart Failure
Open accessAbstract
Background: Although empagliflozin was shown to profoundly reduce cardiovascular events in diabetic patients and blunt the decline in cardiac function in nondiabetic mice with established heart failure (HF), the mechanism of action remains unknown. Methods and Results: We treated 2 rodent models of HF with 10 mg/kg per day empagliflozin and measured activation of the NLRP3 (nucleotide-binding domain-like receptor protein 3) inflammasome in the heart. We show for the first time that beneficial effects of empagliflozin in HF with reduced ejection fraction (HF with reduced ejection fraction [HFrEF]; n=30–34) occur in the absence of changes in circulating ketone bodies, cardiac ketone oxidation, or increased cardiac ATP production. Of note, empagliflozin attenuated activation of the NLRP3 inflammasome and expression of associated markers of sterile inflammation in hearts from mice with HFrEF, implicating reduced cardiac inflammation as a mechanism of empagliflozin that contributes to sustained function in HFrEF in the absence of diabetes mellitus. In addition, we validate that the beneficial cardiac effects of empagliflozin in HF with preserved ejection fraction (HFpEF; n=9–10) are similarly associated with reduced activation of the NLRP3 inflammasome. Lastly, the ability of empagliflozin to reduce inflammation was completely blunted by a calcium (Ca 2+ ) ionophore, suggesting that empagliflozin exerts its benefit upon restoring optimal cytoplasmic Ca 2+ levels in the heart. Conclusions: These data provide evidence that the beneficial cardiac effects of empagliflozin are associated with reduced cardiac inflammation via blunting activation of the NLRP3 inflammasome in a Ca 2+ -dependent manner and hence may be beneficial in treating HF even in the absence of diabetes mellitus.
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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
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2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
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Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
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Self-citationCV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis
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Lopaschuk, G. D., & Verma, S. (2020) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2020.02.004 · Cited by 894
Self-citationThe NLRP3 inflammasome: contributions to inflammation-related diseases
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Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF
Deng, Y., Xie, M., Li, Q., Xu, X., Ou, W., Zhang, Y., Xiao, H., Yu, H., Zheng, Y., Liang, Y., et al. (2021) · Circulation Research · doi:10.1161/circresaha.120.317933 · Cited by 409
Metabolic and Signaling Roles of Ketone Bodies in Health and Disease
Puchalska, P., & Crawford, P. A. (2021) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-111120-111518 · Cited by 282
Dobrev, D., Heijman, J., Hiram, R., Li, N., & Nattel, S. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00759-w · Cited by 268
Metadata
- Authors
- Byrne, N. J., Matsumura, N., Maayah, Z. H., Ferdaoussi, M., Takahara, S., Darwesh, A. M., Levasseur, J. L., Jahng, J. W. S., Vos, D., Parajuli, N., El-Kadi, A. O. S., Braam, B., Young, M. E., Verma, S., Light, P. E., Sweeney, G., Seubert, J. M., & Dyck, J. R. B.
- Venue
- Circulation: Heart Failure
- Published
- 2020-01
- Volume
- 13
- Issue
- 1
- Pages
- e006277-e006277
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- OpenAlex
- W3002400028
- Cited by
- 257
- References
- 80
- FWCI
- 19.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Byrne, N. J., Matsumura, N., Maayah, Z. H., Ferdaoussi, M., Takahara, S., Darwesh, A. M., Levasseur, J. L., Jahng, J. W. S., Vos, D., Parajuli, N., El-Kadi, A. O. S., Braam, B., Young, M. E., Verma, S., Light, P. E., Sweeney, G., Seubert, J. M., & Dyck, J. R. B. (2020). Empagliflozin Blunts Worsening Cardiac Dysfunction Associated With Reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) Inflammasome Activation in Heart Failure. Circulation: Heart Failure. https://doi.org/10.1161/circheartfailure.119.006277
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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.
