Login Register Cart 0
Generic placeholder image

Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial Hypertrophy

Author(s): Zhicheng Gao, Jiaqi Bao, Yilan Hu, Junjie Tu, Lifang Ye and Lihong Wang*

Volume 24, Issue 13, 2023

Published on: 08 September, 2023

Page: [1009 - 1022] Pages: 14

DOI: 10.2174/1389450124666230907115831

Price: $65

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drugs that exert a hypoglycemic effect by blocking the reabsorption of glucose in the proximal renal tubules, thus promoting the excretion of glucose from urine. Their hypoglycemic effect is not dependent on insulin. Increasing data shows that SGLT2 inhibitors improve cardiovascular outcomes in patients with type 2 diabetes. Previous studies have demonstrated that SGLT2 inhibitors can reduce pathological myocardial hypertrophy with or without diabetes, but the exact mechanism remains to be elucidated. To clarify the relationship between SGLT2 inhibitors and pathological myocardial hypertrophy, with a view to providing a reference for the future treatment thereof, this study reviewed the possible mechanisms of SGLT2 inhibitors in attenuating pathological myocardial hypertrophy. We focused specifically on the mechanisms in terms of inflammation, oxidative stress, myocardial fibrosis, mitochondrial function, epicardial lipids, endothelial function, insulin resistance, cardiac hydrogen and sodium exchange, and autophagy.

Next »
Graphical Abstract

[1]
Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 2015; 75(1): 33-59.
[http://dx.doi.org/10.1007/s40265-014-0337-y] [PMID: 25488697]
[2]
Abdul-Ghani MA, Norton L, DeFronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev 2011; 32(4): 515-31.
[http://dx.doi.org/10.1210/er.2010-0029] [PMID: 21606218]
[3]
Bailey CJ. Renal glucose reabsorption inhibitors to treat diabetes. Trends Pharmacol Sci 2011; 32(2): 63-71.
[http://dx.doi.org/10.1016/j.tips.2010.11.011] [PMID: 21211857]
[4]
Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2011 update: A report from the American Heart Association. Circulation 2011; 123(4): e18-e209.
[http://dx.doi.org/10.1161/CIR.0b013e3182009701] [PMID: 21160056]
[5]
Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol 2018; 15(7): 387-407.
[http://dx.doi.org/10.1038/s41569-018-0007-y] [PMID: 29674714]
[6]
Ritchie RH, Abel ED. Basic Mechanisms of Diabetic Heart Disease. Circ Res 2020; 126(11): 1501-25.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.315913] [PMID: 32437308]
[7]
Szwejkowski BR, Gandy SJ, Rekhraj S, et al. Allopurinol reduces left ventricular mass in patients with type 2 diabetes and left ventricular hypertrophy. J Am Coll Cardiol 2013; 62(24): 2284-93.
[http://dx.doi.org/10.1016/j.jacc.2013.07.074] [PMID: 23994420]
[8]
Dawson A, Morris AD, Struthers AD. The epidemiology of left ventricular hypertrophy in type 2 diabetes mellitus. Diabetologia 2005; 48(10): 1971-9.
[http://dx.doi.org/10.1007/s00125-005-1896-y] [PMID: 16094529]
[9]
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373(22): 2117-28.
[http://dx.doi.org/10.1056/NEJMoa1504720] [PMID: 26378978]
[10]
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377(7): 644-57.
[http://dx.doi.org/10.1056/NEJMoa1611925] [PMID: 28605608]
[11]
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380(4): 347-57.
[http://dx.doi.org/10.1056/NEJMoa1812389] [PMID: 30415602]
[12]
Pabel S, Hamdani N, Luedde M, Sossalla S. SGLT2 Inhibitors and Their Mode of Action in Heart Failure—Has the Mystery Been Unravelled? Curr Heart Fail Rep 2021; 18(5): 315-28.
[http://dx.doi.org/10.1007/s11897-021-00529-8] [PMID: 34523061]
[13]
Verma S, Mazer CD, Yan AT, et al. Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease. Circulation 2019; 140(21): 1693-702.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042375] [PMID: 31434508]
[14]
Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: The DAPA-LVH trial. Eur Heart J 2020; 41(36): 3421-32.
[http://dx.doi.org/10.1093/eurheartj/ehaa419] [PMID: 32578850]
[15]
Kusaka H, Koibuchi N, Hasegawa Y, Ogawa H, Kim-Mitsuyama S. Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome. Cardiovasc Diabetol 2016; 15(1): 157.
[http://dx.doi.org/10.1186/s12933-016-0473-7] [PMID: 27835975]
[16]
Zhang QQ, Li GQ, Zhong Y, et al. Empagliflozin improves chronic hypercortisolism-induced abnormal myocardial structure and cardiac function in mice. Ther Adv Chronic Dis 2020; 11
[http://dx.doi.org/10.1177/2040622320974833] [PMID: 33294147]
[17]
Takasu T, Takakura S. Effect of ipragliflozin, an SGLT2 inhibitor, on cardiac histopathological changes in a non-diabetic rat model of cardiomyopathy. Life Sci 2019; 230: 19-27.
[http://dx.doi.org/10.1016/j.lfs.2019.05.051] [PMID: 31125563]
[18]
Depre C, Young ME, Ying J, et al. Streptozotocin-induced changes in cardiac gene expression in the absence of severe contractile dysfunction. J Mol Cell Cardiol 2000; 32(6): 985-96.
[http://dx.doi.org/10.1006/jmcc.2000.1139] [PMID: 10888252]
[19]
Frustaci A, Kajstura J, Chimenti C, et al. Myocardial cell death in human diabetes. Circ Res 2000; 87(12): 1123-32.
[http://dx.doi.org/10.1161/01.RES.87.12.1123] [PMID: 11110769]
[20]
Kumar R, Yong QC, Thomas CM, Baker KM. Review: Intracardiac intracellular angiotensin system in diabetes. Am J Physiol Regul Integr Comp Physiol 2012; 302(5): R510-7.
[http://dx.doi.org/10.1152/ajpregu.00512.2011] [PMID: 22170614]
[21]
Lei S, Li H, Xu J, et al. Hyperglycemia-induced protein kinase C β2 activation induces diastolic cardiac dysfunction in diabetic rats by impairing caveolin-3 expression and Akt/eNOS signaling. Diabetes 2013; 62(7): 2318-28.
[http://dx.doi.org/10.2337/db12-1391] [PMID: 23474486]
[22]
Pappachan JM, Sebastian J, Bino BC, et al. Cardiac autonomic neuropathy in diabetes mellitus: Prevalence, risk factors and utility of corrected QT interval in the ECG for its diagnosis. Postgrad Med J 2008; 84(990): 205-10.
[http://dx.doi.org/10.1136/pgmj.2007.064048] [PMID: 18424578]
[23]
Olshansky B, Sabbah HN, Hauptman PJ, Colucci WS. Parasympathetic nervous system and heart failure: Pathophysiology and potential implications for therapy. Circulation 2008; 118(8): 863-71.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.760405] [PMID: 18711023]
[24]
Bisognano JD, Weinberger HD, Bohlmeyer TJ, et al. Myocardial-directed overexpression of the human beta(1)-adrenergic receptor in transgenic mice. J Mol Cell Cardiol 2000; 32(5): 817-30.
[http://dx.doi.org/10.1006/jmcc.2000.1123] [PMID: 10775486]
[25]
Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol 2013; 1(2): 140-51.
[http://dx.doi.org/10.1016/S2213-8587(13)70050-0] [PMID: 24622320]
[26]
Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: Role in cardiovascular biology and disease. Circ Res 2000; 86(5): 494-501.
[http://dx.doi.org/10.1161/01.RES.86.5.494] [PMID: 10720409]
[27]
Takimoto E, Kass DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension 2007; 49(2): 241-8.
[http://dx.doi.org/10.1161/01.HYP.0000254415.31362.a7]
[28]
Yamamoto E, Lai ZF, Yamashita T, et al. Enhancement of cardiac oxidative stress by tachycardia and its critical role in cardiac hypertrophy and fibrosis. J Hypertens 2006; 24(10): 2057-69.
[http://dx.doi.org/10.1097/01.hjh.0000244956.47114.c1] [PMID: 16957567]
[29]
Komosa A, Rzymski P, Perek B, et al. Platelets redox balance assessment: Current evidence and methodological considerations. Vascul Pharmacol 2017; 93-95: 6-13.
[http://dx.doi.org/10.1016/j.vph.2017.06.002] [PMID: 28684282]
[30]
Takeshima H, Kobayashi N, Koguchi W, Ishikawa M, Sugiyama F, Ishimitsu T. Cardioprotective effect of a combination of Rho-kinase inhibitor and p38 MAPK inhibitor on cardiovascular remodeling and oxidative stress in Dahl rats. J Atheroscler Thromb 2012; 19(4): 326-36.
[http://dx.doi.org/10.5551/jat.11114] [PMID: 22166971]
[31]
Tsutsui H, Ide T, Hayashidani S, et al. Effects of ACE inhibition on left ventricular failure and oxidative stress in Dahl salt-sensitive rats. J Cardiovasc Pharmacol 2001; 37(6): 725-33.
[http://dx.doi.org/10.1097/00005344-200106000-00010] [PMID: 11392469]
[32]
Josephson RA, Silverman HS, Lakatta EG, Stern MD, Zweier JL. Study of the mechanisms of hydrogen peroxide and hydroxyl free radical-induced cellular injury and calcium overload in cardiac myocytes. J Biol Chem 1991; 266(4): 2354-61.
[http://dx.doi.org/10.1016/S0021-9258(18)52251-1] [PMID: 1846625]
[33]
Siwik DA, Tzortzis JD, Pimental DR, et al. Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro. Circ Res 1999; 85(2): 147-53.
[http://dx.doi.org/10.1161/01.RES.85.2.147] [PMID: 10417396]
[34]
Satta S, Mahmoud AM, Wilkinson FL, Yvonne Alexander M, White SJ. The Role of Nrf2 in Cardiovascular Function and Disease. Oxid Med Cell Longev 2017; 2017: 1-18.
[http://dx.doi.org/10.1155/2017/9237263] [PMID: 29104732]
[35]
Li C, Zhang J, Xue M, et al. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovasc Diabetol 2019; 18(1): 15.
[http://dx.doi.org/10.1186/s12933-019-0816-2] [PMID: 30710997]
[36]
Herzig S, Shaw RJ. AMPK: Guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 2018; 19(2): 121-35.
[http://dx.doi.org/10.1038/nrm.2017.95] [PMID: 28974774]
[37]
Kolijn D, Pabel S, Tian Y, et al. Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation. Cardiovasc Res 2021; 117(2): 495-507.
[http://dx.doi.org/10.1093/cvr/cvaa123] [PMID: 32396609]
[38]
Tsai KL, Hsieh PL, Chou WC, Cheng HC, Huang YT, Chan SH. Dapagliflozin attenuates hypoxia/reoxygenation-caused cardiac dysfunction and oxidative damage through modulation of AMPK. Cell Biosci 2021; 11(1): 44.
[http://dx.doi.org/10.1186/s13578-021-00547-y] [PMID: 33637129]
[39]
Kong SS, Liu JJ, Yu XJ, Lu Y, Zang WJ. Protection against ischemia-induced oxidative stress conferred by vagal stimulation in the rat heart: Involvement of the AMPK-PKC pathway. Int J Mol Sci 2012; 13(12): 14311-25.
[http://dx.doi.org/10.3390/ijms131114311] [PMID: 23203066]
[40]
Yurista SR, Silljé HHW, Oberdorf-Maass SU, et al. Sodium–glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail 2019; 21(7): 862-73.
[http://dx.doi.org/10.1002/ejhf.1473] [PMID: 31033127]
[41]
Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2′ -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev 2009; 27(2): 120-39.
[http://dx.doi.org/10.1080/10590500902885684] [PMID: 19412858]
[42]
Sugizaki T, Zhu S, Guo G, et al. Treatment of diabetic mice with the SGLT2 inhibitor TA-1887 antagonizes diabetic cachexia and decreases mortality. NPJ Aging Mech Dis 2017; 3(1): 12.
[http://dx.doi.org/10.1038/s41514-017-0012-0] [PMID: 28900540]
[43]
Heymans S, Corsten MF, Verhesen W, et al. Macrophage microRNA-155 promotes cardiac hypertrophy and failure. Circulation 2013; 128(13): 1420-32.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.001357] [PMID: 23956210]
[44]
Burkly LC, Michaelson JS, Hahm K, Jakubowski A, Zheng TS. TWEAKing tissue remodeling by a multifunctional cytokine: Role of TWEAK/Fn14 pathway in health and disease. Cytokine 2007; 40(1): 1-16.
[http://dx.doi.org/10.1016/j.cyto.2007.09.007] [PMID: 17981048]
[45]
Yerra VG, Batchu SN, Kabir G, et al. Empagliflozin Disrupts a Tnfrsf12a-Mediated Feed Forward Loop That Promotes Left Ventricular Hypertrophy. Cardiovasc Drugs Ther 2022; 36(4): 619-32.
[http://dx.doi.org/10.1007/s10557-021-07190-2] [PMID: 33886003]
[46]
Jain M, Jakubowski A, Cui L, et al. A novel role for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the development of cardiac dysfunction and failure. Circulation 2009; 119(15): 2058-68.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.837286] [PMID: 19349318]
[47]
Novoyatleva T, Janssen W, Wietelmann A, Schermuly RT, Engel FB. TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy. Cytokine 2013; 64(1): 43-5.
[http://dx.doi.org/10.1016/j.cyto.2013.05.009] [PMID: 23764551]
[48]
Chorianopoulos E, Heger T, Lutz M, et al. FGF-inducible 14-kDa protein (Fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappaB activation by TWEAK. Basic Res Cardiol 2010; 105(2): 301-13.
[http://dx.doi.org/10.1007/s00395-009-0046-y] [PMID: 19629561]
[49]
Novoyatleva T, Sajjad A, Engel FB. TWEAK-Fn14 Cytokine-Receptor Axis: A New Player of Myocardial Remodeling and Cardiac Failure. Front Immunol 2014; 5: 50.
[http://dx.doi.org/10.3389/fimmu.2014.00050] [PMID: 24611063]
[50]
Gupta S, Kumar S, Sopko N, Qin Y, Wei C, Kim IK. Thymosin β4 and cardiac protection: Implication in inflammation and fibrosis. Ann N Y Acad Sci 2012; 1269(1): 84-91.
[http://dx.doi.org/10.1111/j.1749-6632.2012.06752.x] [PMID: 23045975]
[51]
Doltra A, Stawowy P, Dietrich T, Schneeweis C, Fleck E, Kelle S. Magnetic resonance imaging of cardiovascular fibrosis and inflammation: From clinical practice to animal studies and back. BioMed Res Int 2013; 2013: 1-10.
[http://dx.doi.org/10.1155/2013/676489] [PMID: 24058912]
[52]
Meléndez GC. Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats. Hypertension 2010; 56(2): 225-31.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.148635]
[53]
Kennedy A, Martinez K, Chuang CC, LaPoint K, McIntosh M. Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: Mechanisms of action and implications. J Nutr 2009; 139(1): 1-4.
[http://dx.doi.org/10.3945/jn.108.098269] [PMID: 19056664]
[54]
He Y, Zhou L, Fan Z, Liu S, Fang W. Palmitic acid, but not high-glucose, induced myocardial apoptosis is alleviated by N-acetylcysteine due to attenuated mitochondrial-derived ROS accumulation-induced endoplasmic reticulum stress. Cell Death Dis 2018; 9(5): 568.
[http://dx.doi.org/10.1038/s41419-018-0593-y] [PMID: 29752433]
[55]
Mangali S, Bhat A, Udumula MP, Dhar I, Sriram D, Dhar A. Inhibition of protein kinase R protects against palmitic acid–induced inflammation, oxidative stress, and apoptosis through the JNK/NF-kB/NLRP3 pathway in cultured H9C2 cardiomyocytes. J Cell Biochem 2019; 120(3): 3651-63.
[http://dx.doi.org/10.1002/jcb.27643] [PMID: 30259999]
[56]
Tang X, Pan L, Zhao S, et al. SNO-MLP (S-Nitrosylation of Muscle LIM Protein) Facilitates Myocardial Hypertrophy Through TLR3 (Toll-Like Receptor 3)–Mediated RIP3 (Receptor-Interacting Protein Kinase 3) and NLRP3 (NOD-Like Receptor Pyrin Domain Containing 3) Inflammasome Activation. Circulation 2020; 141(12): 984-1000.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042336] [PMID: 31902237]
[57]
Moellmann J, Mann PA, Kappel BA, et al. The sodium-glucose co-transporter-2 inhibitor ertugliflozin modifies the signature of cardiac substrate metabolism and reduces cardiac MTOR signalling, endoplasmic reticulum stress and apoptosis. Diabetes Obes Metab 2022; 24(11): 2263-72.
[http://dx.doi.org/10.1111/dom.14814] [PMID: 35801343]
[58]
Heerspink HJL, Perco P, Mulder S, et al. Canagliflozin reduces inflammation and fibrosis biomarkers: A potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia 2019; 62(7): 1154-66.
[http://dx.doi.org/10.1007/s00125-019-4859-4] [PMID: 31001673]
[59]
Andreadou I, Efentakis P, Balafas E, et al. Empagliflozin Limits Myocardial Infarction in vivo and Cell Death in vitro: Role of STAT3, Mitochondria, and Redox Aspects. Front Physiol 2017; 8: 1077.
[http://dx.doi.org/10.3389/fphys.2017.01077] [PMID: 29311992]
[60]
Lin K, Yang N, Luo W, et al. Direct cardio-protection of Dapagliflozin against obesity-related cardiomyopathy via NHE1/MAPK signaling. Acta Pharmacol Sin 2022; 43(10): 2624-35.
[http://dx.doi.org/10.1038/s41401-022-00885-8] [PMID: 35217813]
[61]
Ye Y, Bajaj M, Yang HC, Perez-Polo JR, Birnbaum Y. SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor. Cardiovasc Drugs Ther 2017; 31(2): 119-32.
[http://dx.doi.org/10.1007/s10557-017-6725-2] [PMID: 28447181]
[62]
Byrne NJ, Matsumura N, Maayah ZH, et al. Empagliflozin Blunts Worsening Cardiac Dysfunction Associated With Reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) Inflammasome Activation in Heart Failure. Circ Heart Fail 2020; 13(1): e006277.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006277] [PMID: 31957470]
[63]
Kim SR, Lee SG, Kim SH, et al. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun 2020; 11(1): 2127.
[http://dx.doi.org/10.1038/s41467-020-15983-6] [PMID: 32358544]
[64]
Wang H. CD28/B7 Deficiency Attenuates Systolic Overload-Induced Congestive Heart Failure, Myocardial and Pulmonary Inflammation, and Activated T Cell Accumulation in the Heart and Lungs. Hypertension 2016; 68(3): 688-96.
[65]
Forrester SJ, Booz GW, Sigmund CD, et al. Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology. Physiol Rev 2018; 98(3): 1627-738.
[http://dx.doi.org/10.1152/physrev.00038.2017] [PMID: 29873596]
[66]
Frangogiannis NG. Cardiac fibrosis: Cell biological mechanisms, molecular pathways and therapeutic opportunities. Mol Aspects Med 2019; 65: 70-99.
[http://dx.doi.org/10.1016/j.mam.2018.07.001] [PMID: 30056242]
[67]
Han J. Angiotensin II Causes Biphasic STAT3 Activation Through TLR4 to Initiate Cardiac Remodeling. Hypertension 2018; 72(6): 1301-11.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11860]
[68]
Matsuda S, Umemoto S, Yoshimura K, et al. Angiotensin Activates MCP-1 and Induces Cardiac Hypertrophy and Dysfunction via Toll-like Receptor 4. J Atheroscler Thromb 2015; 22(8): 833-44.
[http://dx.doi.org/10.5551/jat.27292] [PMID: 25752363]
[69]
Kang S, Verma S, Hassanabad AF, et al. Direct Effects of Empagliflozin on Extracellular Matrix Remodelling in Human Cardiac Myofibroblasts: Novel Translational Clues to Explain EMPA-REG OUTCOME Results. Can J Cardiol 2020; 36(4): 543-53.
[http://dx.doi.org/10.1016/j.cjca.2019.08.033] [PMID: 31837891]
[70]
Zhang Y, Lin X, Chu Y, et al. Dapagliflozin: A sodium–glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced cardiac fibrotic remodeling by regulating TGFβ1/Smad signaling. Cardiovasc Diabetol 2021; 20(1): 121.
[http://dx.doi.org/10.1186/s12933-021-01312-8] [PMID: 34116674]
[71]
Aoyama T, Matsui T, Novikov M, Park J, Hemmings B, Rosenzweig A. Serum and glucocorticoid-responsive kinase-1 regulates cardiomyocyte survival and hypertrophic response. Circulation 2005; 111(13): 1652-9.
[http://dx.doi.org/10.1161/01.CIR.0000160352.58142.06] [PMID: 15795328]
[72]
Lang F, Shumilina E. Regulation of ion channels by the serum- and glucocorticoid-inducible kinase SGK1. FASEB J 2013; 27(1): 3-12.
[http://dx.doi.org/10.1096/fj.12-218230] [PMID: 23012321]
[73]
Das S, Aiba T, Rosenberg M, et al. Pathological role of serum- and glucocorticoid-regulated kinase 1 in adverse ventricular remodeling. Circulation 2012; 126(18): 2208-19.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.115592] [PMID: 23019294]
[74]
Habibi J, Aroor AR, Sowers JR, et al. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes. Cardiovasc Diabetol 2017; 16(1): 9.
[http://dx.doi.org/10.1186/s12933-016-0489-z] [PMID: 28086951]
[75]
Sciarretta S, Forte M, Frati G, Sadoshima J. New Insights Into the Role of mTOR Signaling in the Cardiovascular System. Circ Res 2018; 122(3): 489-505.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311147] [PMID: 29420210]
[76]
Sciarretta S, Forte M, Frati G, Sadoshima J. The complex network of mTOR signalling in the heart. Cardiovasc Res 2022; 118(2): 424-39.
[http://dx.doi.org/10.1093/cvr/cvab033] [PMID: 33512477]
[77]
O’Neill BT, Abel ED. Akt1 in the cardiovascular system: Friend or foe? J Clin Invest 2005; 115(8): 2059-64.
[http://dx.doi.org/10.1172/JCI25900] [PMID: 16075047]
[78]
Packer M. SGLT2 Inhibitors Produce Cardiorenal Benefits by Promoting Adaptive Cellular Reprogramming to Induce a State of Fasting Mimicry: A Paradigm Shift in Understanding Their Mechanism of Action. Diabetes Care 2020; 43(3): 508-11.
[http://dx.doi.org/10.2337/dci19-0074] [PMID: 32079684]
[79]
Osataphan S, Macchi C, Singhal G, et al. SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms. JCI Insight 2019; 4(5): e123130.
[http://dx.doi.org/10.1172/jci.insight.123130] [PMID: 30843877]
[80]
Sun X, Han F, Lu Q, et al. Empagliflozin Ameliorates Obesity-Related Cardiac Dysfunction by Regulating Sestrin2-Mediated AMPK-mTOR Signaling and Redox Homeostasis in High-Fat Diet–Induced Obese Mice. Diabetes 2020; 69(6): 1292-305.
[http://dx.doi.org/10.2337/db19-0991] [PMID: 32234722]
[81]
Esposito G, Prasad SVN, Rapacciuolo A, Mao L, Koch WJ, Rockman HA. Cardiac overexpression of a G(q) inhibitor blocks induction of extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase activity in in vivo pressure overload. Circulation 2001; 103(10): 1453-8.
[http://dx.doi.org/10.1161/01.CIR.103.10.1453] [PMID: 11245652]
[82]
Shi L, Zhu D, Wang S, Jiang A, Li F. Dapagliflozin Attenuates Cardiac Remodeling in Mice Model of Cardiac Pressure Overload. Am J Hypertens 2019; 32(5): 452-9.
[http://dx.doi.org/10.1093/ajh/hpz016] [PMID: 30689697]
[83]
Packer M. Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium. J Am Coll Cardiol 2018; 71(20): 2360-72.
[http://dx.doi.org/10.1016/j.jacc.2018.03.509] [PMID: 29773163]
[84]
Venteclef N, Guglielmi V, Balse E, et al. Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur Heart J 2015; 36(13): 795-805.
[http://dx.doi.org/10.1093/eurheartj/eht099] [PMID: 23525094]
[85]
Ng ACT, Strudwick M, van der Geest RJ, et al. Impact of Epicardial Adipose Tissue, Left Ventricular Myocardial Fat Content, and Interstitial Fibrosis on Myocardial Contractile Function. Circ Cardiovasc Imaging 2018; 11(8): e007372.
[http://dx.doi.org/10.1161/CIRCIMAGING.117.007372] [PMID: 30354491]
[86]
Iacobellis G, Gra-Menendez S. Effects of Dapagliflozin on Epicardial Fat Thickness in Patients with Type 2 Diabetes and Obesity. Obesity (Silver Spring) 2020; 28(6): 1068-74.
[http://dx.doi.org/10.1002/oby.22798] [PMID: 32352644]
[87]
Yagi S, Hirata Y, Ise T, et al. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol Metab Syndr 2017; 9(1): 78.
[http://dx.doi.org/10.1186/s13098-017-0275-4] [PMID: 29034006]
[88]
Fukuda T, Bouchi R, Terashima M, et al. Ipragliflozin Reduces Epicardial Fat Accumulation in Non-Obese Type 2 Diabetic Patients with Visceral Obesity: A Pilot Study. Diabetes Ther 2017; 8(4): 851-61.
[http://dx.doi.org/10.1007/s13300-017-0279-y] [PMID: 28616806]
[89]
Bouchi R, Terashima M, Sasahara Y, et al. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: A pilot study. Cardiovasc Diabetol 2017; 16(1): 32.
[http://dx.doi.org/10.1186/s12933-017-0516-8] [PMID: 28253918]
[90]
Requena-Ibáñez JA, Santos-Gallego CG, Rodriguez-Cordero A, et al. Mechanistic Insights of Empagliflozin in Nondiabetic Patients With HFrEF. JACC Heart Fail 2021; 9(8): 578-89.
[http://dx.doi.org/10.1016/j.jchf.2021.04.014] [PMID: 34325888]
[91]
Díaz-Rodríguez E, Agra RM, Fernández ÁL, et al. Effects of dapagliflozin on human epicardial adipose tissue: Modulation of insulin resistance, inflammatory chemokine production, and differentiation ability. Cardiovasc Res 2018; 114(2): 336-46.
[http://dx.doi.org/10.1093/cvr/cvx186] [PMID: 29016744]
[92]
Sato T, Aizawa Y, Yuasa S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol 2018; 17(1): 6.
[http://dx.doi.org/10.1186/s12933-017-0658-8] [PMID: 29301516]
[93]
Madani S, Degirolamo S, Muñoz D, Li R, Sweeney G. Direct effects of leptin on size and extracellular matrix components of human pediatric ventricular myocytes. Cardiovasc Res 2006; 69(3): 716-25.
[http://dx.doi.org/10.1016/j.cardiores.2005.11.022] [PMID: 16376323]
[94]
Iacobellis G, Diaz S, Mendez A, Goldberg R. Increased epicardial fat and plasma leptin in type 1 diabetes independently of obesity. Nutr Metab Cardiovasc Dis 2014; 24(7): 725-9.
[http://dx.doi.org/10.1016/j.numecd.2013.11.001] [PMID: 24368079]
[95]
Rajapurohitam V, Gan XT, Kirshenbaum LA, Karmazyn M. The obesity-associated peptide leptin induces hypertrophy in neonatal rat ventricular myocytes. Circ Res 2003; 93(4): 277-9.
[http://dx.doi.org/10.1161/01.RES.0000089255.37804.72] [PMID: 12893740]
[96]
Xu FP, Chen MS, Wang YZ, et al. Leptin induces hypertrophy via endothelin-1-reactive oxygen species pathway in cultured neonatal rat cardiomyocytes. Circulation 2004; 110(10): 1269-75.
[http://dx.doi.org/10.1161/01.CIR.0000140766.52771.6D] [PMID: 15313952]
[97]
Huby AC, Antonova G, Groenendyk J, et al. Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis. Circulation 2015; 132(22): 2134-45.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.018226] [PMID: 26362633]
[98]
Packer M. Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis. Diabetes Obes Metab 2018; 20(6): 1361-6.
[http://dx.doi.org/10.1111/dom.13229] [PMID: 29359851]
[99]
Teta D, Bevington A, Brown J, Pawluczyk I, Harris K, Walls J. Acidosis downregulates leptin production from cultured adipocytes through a glucose transport-dependent post-transcriptional mechanism. J Am Soc Nephrol 2003; 14(9): 2248-54.
[http://dx.doi.org/10.1097/01.ASN.0000083903.18724.93] [PMID: 12937300]
[100]
Miura H, Sakaguchi K, Okada Y, et al. Effects of ipragliflozin on glycemic control, appetite and its related hormones: A prospective, multicenter, open-label study (SOAR-KOBE Study). J Diabetes Investig 2019; 10(5): 1254-61.
[http://dx.doi.org/10.1111/jdi.13015] [PMID: 30688412]
[101]
Wu P. Systematic Review and Meta-Analysis of Randomized Controlled Trials on the Effect of SGLT2 Inhibitor on Blood Leptin and Adiponectin Level in Patients with Type 2 Diabetes. Horm Metab Res 2019; 51(8): 487-94.
[http://dx.doi.org/10.1055/a-0958-2441]
[102]
Pruett JE, Torres Fernandez ED, Everman SJ, et al. Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome. Int J Mol Sci 2021; 22(5): 2576.
[http://dx.doi.org/10.3390/ijms22052576] [PMID: 33806551]
[103]
Abel ED, Doenst T. Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovasc Res 2011; 90(2): 234-42.
[http://dx.doi.org/10.1093/cvr/cvr015] [PMID: 21257612]
[104]
Rosca MG, Hoppel CL. Mitochondria in heart failure. Cardiovasc Res 2010; 88(1): 40-50.
[http://dx.doi.org/10.1093/cvr/cvq240] [PMID: 20668004]
[105]
Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL. Mitochondrial dysfunction in cardiac disease: Ischemia--reperfusion, aging, and heart failure. J Mol Cell Cardiol 2001; 33(6): 1065-89.
[http://dx.doi.org/10.1006/jmcc.2001.1378] [PMID: 11444914]
[106]
Wang J, Huang X, Liu H, et al. Empagliflozin Ameliorates Diabetic Cardiomyopathy via Attenuating Oxidative Stress and Improving Mitochondrial Function. Oxid Med Cell Longev 2022; 2022: 1-16.
[http://dx.doi.org/10.1155/2022/1122494] [PMID: 35585884]
[107]
Bertero E, Prates Roma L, Ameri P, Maack C. Cardiac effects of SGLT2 inhibitors: The sodium hypothesis. Cardiovasc Res 2018; 114(1): 12-8.
[http://dx.doi.org/10.1093/cvr/cvx149] [PMID: 29016751]
[108]
Baartscheer A, Schumacher CA, Wüst RCI, et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia 2017; 60(3): 568-73.
[http://dx.doi.org/10.1007/s00125-016-4134-x] [PMID: 27752710]
[109]
Bertero E, Maack C. Calcium Signaling and Reactive Oxygen Species in Mitochondria. Circ Res 2018; 122(10): 1460-78.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.310082] [PMID: 29748369]
[110]
Zhou H, Wang S, Zhu P, Hu S, Chen Y, Ren J. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission. Redox Biol 2018; 15: 335-46.
[http://dx.doi.org/10.1016/j.redox.2017.12.019] [PMID: 29306791]
[111]
Tanajak P, Sa-nguanmoo P, Sivasinprasasn S, et al. Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury. J Endocrinol 2018; 236(2): 69-84.
[http://dx.doi.org/10.1530/JOE-17-0457] [PMID: 29142025]
[112]
Shao Q, Meng L, Lee S, et al. Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats. Cardiovasc Diabetol 2019; 18(1): 165.
[http://dx.doi.org/10.1186/s12933-019-0964-4] [PMID: 31779619]
[113]
Wakabayashi S, Hisamitsu T, Nakamura TY. Regulation of the cardiac Na+/H+ exchanger in health and disease. J Mol Cell Cardiol 2013; 61: 68-76.
[http://dx.doi.org/10.1016/j.yjmcc.2013.02.007] [PMID: 23429007]
[114]
Xue J, Mraiche F, Zhou D, et al. Elevated myocardial Na + /H + exchanger isoform 1 activity elicits gene expression that leads to cardiac hypertrophy. Physiol Genomics 2010; 42(3): 374-83.
[http://dx.doi.org/10.1152/physiolgenomics.00064.2010] [PMID: 20460605]
[115]
Yeves AM, Ennis IL. Na+/H+ exchanger and cardiac hypertrophy. Hipertens Riesgo Vasc 2020; 37(1): 22-32.
[http://dx.doi.org/10.1016/j.hipert.2019.09.002] [PMID: 31601481]
[116]
Anzawa R, Seki S, Nagoshi T, Taniguchi I, Feuvray D, Yoshimura M. The role of Na+/H+ exchanger in Ca2+ overload and ischemic myocardial damage in hearts from type 2 diabetic db/db mice. Cardiovasc Diabetol 2012; 11(1): 33.
[http://dx.doi.org/10.1186/1475-2840-11-33] [PMID: 22490613]
[117]
Darmellah A, Baetz D, Prunier F, Tamareille S, Rücker-Martin C, Feuvray D. Enhanced activity of the myocardial Na+/H+ exchanger contributes to left ventricular hypertrophy in the Goto–Kakizaki rat model of type 2 diabetes: Critical role of Akt. Diabetologia 2007; 50(6): 1335-44.
[http://dx.doi.org/10.1007/s00125-007-0628-x] [PMID: 17429605]
[118]
Nakamura TY, Iwata Y, Arai Y, Komamura K, Wakabayashi S. Activation of Na+/H+ exchanger 1 is sufficient to generate Ca2+ signals that induce cardiac hypertrophy and heart failure. Circ Res 2008; 103(8): 891-9.
[http://dx.doi.org/10.1161/CIRCRESAHA.108.175141] [PMID: 18776042]
[119]
Abdulrahman N, Ibrahim M, Joseph JM, et al. Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression. Mol Cell Biochem 2022; 477(6): 1865-72.
[http://dx.doi.org/10.1007/s11010-022-04411-6] [PMID: 35334035]
[120]
Watkins SJ, Borthwick GM, Oakenfull R, Robson A, Arthur HM. Angiotensin II-induced cardiomyocyte hypertrophy in vitro is TAK1-dependent and Smad2/3-independent. Hypertens Res 2012; 35(4): 393-8.
[http://dx.doi.org/10.1038/hr.2011.196] [PMID: 22072105]
[121]
Jaballah M, Mohamed IA, Alemrayat B, Al-Sulaiti F, Mlih M, Mraiche F. Na+/H+ exchanger isoform 1 induced cardiomyocyte hypertrophy involves activation of p90 ribosomal s6 kinase. PLoS One 2015; 10(4): e0122230.
[http://dx.doi.org/10.1371/journal.pone.0122230] [PMID: 25830299]
[122]
Baartscheer A, Schumacher C, Vanborren M, et al. Chronic inhibition of Na/H-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure. Cardiovasc Res 2005; 65(1): 83-92.
[http://dx.doi.org/10.1016/j.cardiores.2004.09.024] [PMID: 15621036]
[123]
Kusumoto K, Haist JV, Karmazyn M. Na + /H + exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats. Am J Physiol Heart Circ Physiol 2001; 280(2): H738-45.
[http://dx.doi.org/10.1152/ajpheart.2001.280.2.H738] [PMID: 11158973]
[124]
Uthman L, Baartscheer A, Bleijlevens B, et al. Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: Inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation. Diabetologia 2018; 61(3): 722-6.
[http://dx.doi.org/10.1007/s00125-017-4509-7] [PMID: 29197997]
[125]
Spigoni V, Fantuzzi F, Carubbi C, et al. Sodium-glucose cotransporter 2 inhibitors antagonize lipotoxicity in human myeloid angiogenic cells and ADP-dependent activation in human platelets: Potential relevance to prevention of cardiovascular events. Cardiovasc Diabetol 2020; 19(1): 46.
[http://dx.doi.org/10.1186/s12933-020-01016-5] [PMID: 32264868]
[126]
Yang C-C, et al. Early administration of empagliflozin preserved heart function in cardiorenal syndrome in rat. Biomed Pharmacother 2019; 109(8): 658-70.
[http://dx.doi.org/10.1016/j.biopha.2018.10.095]
[127]
Ye Y, Jia X, Bajaj M, Birnbaum Y. Dapagliflozin Attenuates Na+/H+ Exchanger-1 in Cardiofibroblasts via AMPK Activation. Cardiovasc Drugs Ther 2018; 32(6): 553-8.
[http://dx.doi.org/10.1007/s10557-018-6837-3] [PMID: 30367338]
[128]
Tian J, Zhang M, Suo M, et al. Dapagliflozin alleviates cardiac fibrosis through suppressing EndMT and fibroblast activation via AMPKα/TGF-β/Smad signalling in type 2 diabetic rats. J Cell Mol Med 2021; 25(16): 7642-59.
[http://dx.doi.org/10.1111/jcmm.16601] [PMID: 34169635]
[129]
Hasan R, Lasker S, Hasan A, et al. Canagliflozin ameliorates renal oxidative stress and inflammation by stimulating AMPK–Akt–eNOS pathway in the isoprenaline-induced oxidative stress model. Sci Rep 2020; 10(1): 14659.
[http://dx.doi.org/10.1038/s41598-020-71599-2] [PMID: 32887916]
[130]
Paternostro G, Pagano D, Gnecchi-Ruscone T, Bonser RS, Camici PG. Insulin resistance in patients with cardiac hypertrophy. Cardiovasc Res 1999; 42(1): 246-53.
[http://dx.doi.org/10.1016/S0008-6363(98)00233-8] [PMID: 10435017]
[131]
Jia G, Hill MA, Sowers JR. Diabetic Cardiomyopathy. Circ Res 2018; 122(4): 624-38.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311586] [PMID: 29449364]
[132]
Sundgren NC, Giraud GD, Schultz JM, Lasarev MR, Stork PJS, Thornburg KL. Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes. Am J Physiol Regul Integr Comp Physiol 2003; 285(6): R1481-9.
[http://dx.doi.org/10.1152/ajpregu.00232.2003] [PMID: 12947030]
[133]
Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2014; 124(2): 499-508.
[http://dx.doi.org/10.1172/JCI72227] [PMID: 24463454]
[134]
Mudaliar S, Henry RR, Boden G, et al. Changes in insulin sensitivity and insulin secretion with the sodium glucose cotransporter 2 inhibitor dapagliflozin. Diabetes Technol Ther 2014; 16(3): 137-44.
[http://dx.doi.org/10.1089/dia.2013.0167] [PMID: 24237386]
[135]
Scheen AJ, Paquot N. Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence. Diabetes Metab 2014; 40(6) (Suppl. 1): S4-S11.
[http://dx.doi.org/10.1016/S1262-3636(14)72689-8] [PMID: 25554070]
[136]
Hammoudi N, Jeong D, Singh R, et al. Empagliflozin Improves Left Ventricular Diastolic Dysfunction in a Genetic Model of Type 2 Diabetes. Cardiovasc Drugs Ther 2017; 31(3): 233-46.
[http://dx.doi.org/10.1007/s10557-017-6734-1] [PMID: 28643218]
[137]
Murdoch CE, Chaubey S, Zeng L, et al. Endothelial NADPH oxidase-2 promotes interstitial cardiac fibrosis and diastolic dysfunction through proinflammatory effects and endothelial-mesenchymal transition. J Am Coll Cardiol 2014; 63(24): 2734-41.
[http://dx.doi.org/10.1016/j.jacc.2014.02.572] [PMID: 24681145]
[138]
Juni RP, Kuster DWD, Goebel M, et al. Cardiac Microvascular Endothelial Enhancement of Cardiomyocyte Function Is Impaired by Inflammation and Restored by Empagliflozin. JACC Basic Transl Sci 2019; 4(5): 575-91.
[http://dx.doi.org/10.1016/j.jacbts.2019.04.003] [PMID: 31768475]
[139]
Rahadian A, Fukuda D, Salim HM, et al. Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice. J Atheroscler Thromb 2020; 27(11): 1141-51.
[http://dx.doi.org/10.5551/jat.52100] [PMID: 32101837]
[140]
Pabel S, Wagner S, Bollenberg H, et al. Empagliflozin directly improves diastolic function in human heart failure. Eur J Heart Fail 2018; 20(12): 1690-700.
[http://dx.doi.org/10.1002/ejhf.1328] [PMID: 30328645]
[141]
Salim HM, Fukuda D, Yagi S, Soeki T, Shimabukuro M, Sata M. Glycemic Control with Ipragliflozin, a Novel Selective SGLT2 Inhibitor, Ameliorated Endothelial Dysfunction in Streptozotocin-Induced Diabetic Mouse. Front Cardiovasc Med 2016; 3: 43.
[http://dx.doi.org/10.3389/fcvm.2016.00043] [PMID: 27833913]
[142]
Lee DM, Battson ML, Jarrell DK, et al. SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice. Cardiovasc Diabetol 2018; 17(1): 62.
[http://dx.doi.org/10.1186/s12933-018-0708-x] [PMID: 29703207]
[143]
Levine B, Packer M, Codogno P. Development of autophagy inducers in clinical medicine. J Clin Invest 2015; 125(1): 14-24.
[http://dx.doi.org/10.1172/JCI73938] [PMID: 25654546]
[144]
Levine B, Kroemer G. Biological Functions of Autophagy Genes: A Disease Perspective. Cell 2019; 176(1-2): 11-42.
[http://dx.doi.org/10.1016/j.cell.2018.09.048] [PMID: 30633901]
[145]
Dutta D, Xu J, Kim JS, Dunn WA Jr, Leeuwenburgh C. Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity. Autophagy 2013; 9(3): 328-44.
[http://dx.doi.org/10.4161/auto.22971] [PMID: 23298947]
[146]
Packer M. Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: Implications for understanding the effects of current and future treatments for heart failure. Eur Heart J 2020; 41(39): 3856-61.
[http://dx.doi.org/10.1093/eurheartj/ehaa360] [PMID: 32460327]
[147]
Alcendor RR, Gao S, Zhai P, et al. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res 2007; 100(10): 1512-21.
[http://dx.doi.org/10.1161/01.RES.0000267723.65696.4a] [PMID: 17446436]
[148]
Tanno M, Kuno A, Yano T, et al. Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem 2010; 285(11): 8375-82.
[http://dx.doi.org/10.1074/jbc.M109.090266] [PMID: 20089851]
[149]
Ma S, Feng J, Zhang R, et al. SIRT1 Activation by Resveratrol Alleviates Cardiac Dysfunction via Mitochondrial Regulation in Diabetic Cardiomyopathy Mice. Oxid Med Cell Longev 2017; 2017: 1-15.
[http://dx.doi.org/10.1155/2017/4602715] [PMID: 28883902]
[150]
Bugyei-Twum A, Ford C, Civitarese R, et al. Sirtuin 1 activation attenuates cardiac fibrosis in a rodent pressure overload model by modifying Smad2/3 transactivation. Cardiovasc Res 2018; 114(12): 1629-41.
[http://dx.doi.org/10.1093/cvr/cvy131] [PMID: 29800064]
[151]
Packer M. Cardioprotective Effects of Sirtuin-1 and Its Downstream Effectors. Circ Heart Fail 2020; 13(9): e007197.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007197] [PMID: 32894987]
[152]
Kanamori H, Takemura G, Goto K, et al. Autophagic adaptations in diabetic cardiomyopathy differ between type 1 and type 2 diabetes. Autophagy 2015; 11(7): 1146-60.
[http://dx.doi.org/10.1080/15548627.2015.1051295] [PMID: 26042865]
[153]
Krzysiak TC, Thomas L, Choi YJ, et al. An Insulin-Responsive Sensor in the SIRT1 Disordered Region Binds DBC1 and PACS-2 to Control Enzyme Activity. Mol Cell 2018; 72(6): 985-998.e7.
[http://dx.doi.org/10.1016/j.molcel.2018.10.007] [PMID: 30415949]
[154]
Paula-Gomes S. nsulin suppresses atrophy- and autophagy-related genes in heart tissue and cardiomyocytes through AKT/FOXO signaling. Horm Metab Res 2013; 45(12): 849-55.
[155]
Dewanjee S, Vallamkondu J, Kalra RS, John A, Reddy PH, Kandimalla R. Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy. Ageing Res Rev 2021; 68: 101338.
[http://dx.doi.org/10.1016/j.arr.2021.101338] [PMID: 33838320]
[156]
Packer M. Autophagy-dependent and -independent modulation of oxidative and organellar stress in the diabetic heart by glucose-lowering drugs. Cardiovasc Diabetol 2020; 19(1): 62.
[http://dx.doi.org/10.1186/s12933-020-01041-4] [PMID: 32404204]
[157]
Packer M. Autophagy stimulation and intracellular sodium reduction as mediators of the cardioprotective effect of sodium–glucose cotransporter 2 inhibitors. Eur J Heart Fail 2020; 22(4): 618-28.
[http://dx.doi.org/10.1002/ejhf.1732] [PMID: 32037659]
[158]
Umino H, Hasegawa K, Minakuchi H, et al. High Basolateral Glucose Increases Sodium-Glucose Cotransporter 2 and Reduces Sirtuin-1 in Renal Tubules through Glucose Transporter-2 Detection. Sci Rep 2018; 8(1): 6791.
[http://dx.doi.org/10.1038/s41598-018-25054-y] [PMID: 29717156]
[159]
Swe MT. Dapagliflozin not only improves hepatic injury and pancreatic endoplasmic reticulum stress, but also induces hepatic gluconeogenic enzymes expression in obese rats. Clin Sci 2019; 133(23): 2415-30.
[http://dx.doi.org/10.1042/CS20190863]
[160]
Sasaki M, Sasako T, Kubota N, et al. Dual Regulation of Gluconeogenesis by Insulin and Glucose in the Proximal Tubules of the Kidney. Diabetes 2017; 66(9): 2339-50.
[http://dx.doi.org/10.2337/db16-1602] [PMID: 28630133]
[161]
Kim J-W, et al. Effect of sodium-glucose cotransporter 2 inhibitor, empagliflozin, and α-glucosidase inhibitor, voglibose, on hepatic steatosis in an animal model of type 2 diabetes. J Cell Biochem 2018.
[PMID: 30474134]
[162]
Ying Y, Jiang C, Zhang M, Jin J, Ge S, Wang X. Phloretin protects against cardiac damage and remodeling via restoring SIRT1 and anti-inflammatory effects in the streptozotocin-induced diabetic mouse model. Aging (Albany NY) 2019; 11(9): 2822-35.
[http://dx.doi.org/10.18632/aging.101954] [PMID: 31076562]
[163]
Lee JY, Lee M, Lee JY, et al. Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway. Diabetes Metab J 2021; 45(6): 921-32.
[http://dx.doi.org/10.4093/dmj.2020.0187] [PMID: 33611885]
[164]
Suga T, Sato K, Ohyama T, et al. Ipragliflozin-induced improvement of liver steatosis in obese mice may involve sirtuin signaling. World J Hepatol 2020; 12(7): 350-62.
[http://dx.doi.org/10.4254/wjh.v12.i7.350] [PMID: 32821334]
[165]
Hawley SA, Ford RJ, Smith BK, et al. The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels. Diabetes 2016; 65(9): 2784-94.
[http://dx.doi.org/10.2337/db16-0058] [PMID: 27381369]
[166]
Mancini SJ, Boyd D, Katwan OJ, et al. Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms. Sci Rep 2018; 8(1): 5276.
[http://dx.doi.org/10.1038/s41598-018-23420-4] [PMID: 29588466]
[167]
Aragón-Herrera A, Feijóo-Bandín S, Otero Santiago M, et al. Empagliflozin reduces the levels of CD36 and cardiotoxic lipids while improving autophagy in the hearts of Zucker diabetic fatty rats. Biochem Pharmacol 2019; 170: 113677.
[http://dx.doi.org/10.1016/j.bcp.2019.113677] [PMID: 31647926]
[168]
Mizuno M, Kuno A, Yano T, et al. Empagliflozin normalizes the size and number of mitochondria and prevents reduction in mitochondrial size after myocardial infarction in diabetic hearts. Physiol Rep 2018; 6(12): e13741.
[http://dx.doi.org/10.14814/phy2.13741] [PMID: 29932506]
[169]
Xu C, Wang W, Zhong J, et al. Canagliflozin exerts anti-inflammatory effects by inhibiting intracellular glucose metabolism and promoting autophagy in immune cells. Biochem Pharmacol 2018; 152: 45-59.
[http://dx.doi.org/10.1016/j.bcp.2018.03.013] [PMID: 29551587]
[170]
Lee YH, Kim SH, Kang JM, et al. Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy. Am J Physiol Renal Physiol 2019; 317(4): F767-80.
[http://dx.doi.org/10.1152/ajprenal.00565.2018] [PMID: 31390268]
[171]
Adingupu DD, Göpel SO, Grönros J, et al. SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/ob−/− mice. Cardiovasc Diabetol 2019; 18(1): 16.
[http://dx.doi.org/10.1186/s12933-019-0820-6] [PMID: 30732594]
[172]
Maillet M, van Berlo JH, Molkentin JD. Molecular basis of physiological heart growth: Fundamental concepts and new players. Nat Rev Mol Cell Biol 2013; 14(1): 38-48.
[http://dx.doi.org/10.1038/nrm3495] [PMID: 23258295]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy