β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β

References

• Cho DH, Yoo BS. Current prevalence, incidence, and outcomes of heart failure with preserved ejection fraction. Heart Fail Clin. 2021;17(3):315–326. doi:10.1016/j.hfc.2021.03.002
   PubMed Web of Science ®Google Scholar
• Steinberg BA, Zhao X, Heidenreich PA, et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012;126(1):65–75. doi:10.1161/CIRCULATIONAHA.111.080770
   PubMed Web of Science ®Google Scholar
• Shah SJ, Kitzman DW, Borlaug BA, et al. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation. 2016;134(1):73–90. doi:10.1161/CIRCULATIONAHA.116.021884
   PubMed Web of Science ®Google Scholar
• Gevaert AB, Boen JRA, Segers VF, et al. Heart failure with preserved ejection fraction: a review of cardiac and noncardiac pathophysiology. Front Physiol. 2019;10:638. doi:10.3389/fphys.2019.00638
   PubMed Web of Science ®Google Scholar
• Gentile F, Ghionzoli N, Borrelli C, et al. Epidemiological and clinical boundaries of heart failure with preserved ejection fraction. Eur J Prev Cardiol. 2021;zwab077. doi:10.1093/eurjpc/zwab077
   PubMed Web of Science ®Google Scholar
• Youm YH, Nguyen KY, Grant RW, et al. The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015;21(3):263–269. doi:10.1038/nm.3804
   PubMed Web of Science ®Google Scholar
• Chang PV, Hao L, Offermanns S, et al. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014;111(6):2247–2252. doi:10.1073/pnas.1322269111
   PubMed Web of Science ®Google Scholar
• Bedi KC, Snyder NW, Brandimarto J, et al. Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation. 2016;133(8):706–716. doi:10.1161/CIRCULATIONAHA.115.017545
   PubMed Web of Science ®Google Scholar
• Lopaschuk GD, Ussher JR. Evolving concepts of myocardial energy metabolism: more than just fats and carbohydrates. Circ Res. 2016;119(11):1173–1176. doi:10.1161/CIRCRESAHA.116.310078
   PubMed Web of Science ®Google Scholar
• Byrne NJ, Soni S, Takahara S, et al. Chronically elevating circulating ketones can reduce cardiac inflammation and blunt the development of heart failure. Circ Heart Fail. 2020;13(6):e006573. doi:10.1161/CIRCHEARTFAILURE.119.006573
   PubMed Web of Science ®Google Scholar
• Butler J, Hamo CE, Filippatos G, et al. The potential role and rationale for treatment of heart failure with sodium-glucose co-transporter 2 inhibitors. Eur J Heart Fail. 2017;19(11):1390–1400. doi:10.1002/ejhf.933
   PubMed Web of Science ®Google Scholar
• Nielsen R, Moller N, Gormsen LC, et al. Cardiovascular effects of treatment with the ketone body 3-hydroxybutyrate in chronic heart failure patients. Circulation. 2019;139(18):2129–2141. doi:10.1161/CIRCULATIONAHA.118.036459
   PubMed Web of Science ®Google Scholar
• Deng Y, Xie M, Li Q, et al. Targeting mitochondria-inflammation circuit by beta-hydroxybutyrate mitigates HFpEF. Circ Res. 2021;128(2):232–245. doi:10.1161/CIRCRESAHA.120.317933
   PubMed Web of Science ®Google Scholar
• Schiattarella GG, Altamirano F, Tong D, et al. Nitrosative stress drives heart failure with preserved ejection fraction. Nature. 2019;568(7752):351–356. doi:10.1038/s41586-019-1100-z
   PubMed Web of Science ®Google Scholar
• Liu H, Wang L, Pan Y, et al. Celastrol alleviates aortic valve calcification via inhibition of NADPH oxidase 2 in valvular interstitial cells. JACC Basic Transl Sci. 2020;5(1):35–49. doi:10.1016/j.jacbts.2019.10.004
   PubMedGoogle Scholar
• Hirotani S, Zhai P, Tomita H, et al. Inhibition of glycogen synthase kinase 3beta during heart failure is protective. Circ Res. 2007;101(11):1164–1174. doi:10.1161/CIRCRESAHA.107.160614
   PubMed Web of Science ®Google Scholar
• Horton JL, Davidson MT, Kurishima C, et al. The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense. JCI Insight. 2019;4(4):e124079. doi:10.1172/jci.insight.124079
   PubMed Web of Science ®Google Scholar
• Aubert G, Martin OJ, Horton JL, et al. The failing heart relies on ketone bodies as a fuel. Circulation. 2016;133(8):698–705. doi:10.1161/CIRCULATIONAHA.115.017355
   PubMed Web of Science ®Google Scholar
• Yurista SR, Matsuura TR, Sillje HHW, et al. Ketone ester treatment improves cardiac function and reduces pathologic remodeling in preclinical models of heart failure. Circ Heart Fail. 2021;14(1):e007684. doi:10.1161/CIRCHEARTFAILURE.120.007684
   PubMed Web of Science ®Google Scholar
• Ho KL, Zhang L, Wagg C, et al. Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency. Cardiovasc Res. 2019;115(11):1606–1616. doi:10.1093/cvr/cvz045
   PubMed Web of Science ®Google Scholar
• Han YM, Ramprasath T, Zou MH. beta-hydroxybutyrate and its metabolic effects on age-associated pathology. Exp Mol Med. 2020;52(4):548–555. doi:10.1038/s12276-020-0415-z
   PubMed Web of Science ®Google Scholar
• Nagao M, Toh R, Irino Y, et al. beta-Hydroxybutyrate elevation as a compensatory response against oxidative stress in cardiomyocytes. Biochem Biophys Res Commun. 2016;475(4):322–328. doi:10.1016/j.bbrc.2016.05.097
   PubMed Web of Science ®Google Scholar
• Bansal SS, Ismahil MA, Goel M, et al. Activated T lymphocytes are essential drivers of pathological remodeling in ischemic heart failure. Circ Heart Fail. 2017;10(3):e003688. doi:10.1161/CIRCHEARTFAILURE.116.003688
   PubMed Web of Science ®Google Scholar
• Li N, Bian H, Zhang J, et al. The Th17/Treg imbalance exists in patients with heart failure with normal ejection fraction and heart failure with reduced ejection fraction. Clin Chim Acta. 2010;411(23–24):1963–1968. doi:10.1016/j.cca.2010.08.013
   PubMed Web of Science ®Google Scholar
• Lu M, Qin X, Yao J, et al. Th17/Treg imbalance modulates rat myocardial fibrosis and heart failure by regulating LOX expression. Acta Physiol (Oxf). 2020;230(3):e13537. doi:10.1111/apha.13537
   PubMed Web of Science ®Google Scholar
• Emmerson A, Trevelin SC, Mongue-Din H, et al. Nox2 in regulatory T cells promotes angiotensin II-induced cardiovascular remodeling. J Clin Invest. 2018;128(7):3088–3101. doi:10.1172/JCI97490
   PubMed Web of Science ®Google Scholar
• Hardt SE, Sadoshima J. Glycogen synthase kinase-3beta: a novel regulator of cardiac hypertrophy and development. Circ Res. 2002;90(10):1055–1063. doi:10.1161/01.res.0000018952.70505.f1
   PubMed Web of Science ®Google Scholar
• Haq S, Choukroun G, Lim H, et al. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure. Circulation. 2001;103(5):670–677. doi:10.1161/01.cir.103.5.670
   PubMed Web of Science ®Google Scholar
• Matsuda T, Zhai P, Maejima Y, et al. Distinct roles of GSK-3alpha and GSK-3beta phosphorylation in the heart under pressure overload. Proc Natl Acad Sci U S A. 2008;105(52):20900–20905. doi:10.1073/pnas.0808315106
   PubMed Web of Science ®Google Scholar