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Sodium-glucose co-transporter inhibitors (SGLTis) are the latest class of anti-hyperglycemic agents. In addition to inhibiting the absorption of glucose by the kidney causing glycosuria, these drugs also demonstrate cardio-renal benefits in diabetic subjects. miR-30 family, one of the most abundant microRNAs in the heart, has recently been linked to a setting of cardiovascular diseases and has been proposed as novel biomarkers in kidney dysfunctions as well; their expression is consistently dysregulated in a variety of cardio-renal dysfunctions. The mechanistic involvement and the potential interplay between miR-30 and SGLT2i effects have yet to be thoroughly elucidated. Recent research has stressed the relevance of this cluster of microRNAs as modulators of several pathological processes in the heart and kidneys, raising the possibility of these small ncRNAs playing a central role in various cardiovascular complications, notably, endothelial dysfunction and pathological remodeling. Here, we review current evidence supporting the pleiotropic effects of SGLT2is in cardiovascular and renal outcomes and investigate the link and the coordinated implication of the miR-30 family in endothelial dysfunction and cardiac remodeling. We also discuss the emerging role of circulating miR-30 as non-invasive biomarkers and attractive therapeutic targets for cardiovascular diseases and kidney diseases. Clinical evidence, as well as metabolic, cellular, and molecular aspects, are comprehensively covered.
Alam S, Hasan MK, Neaz S, Hussain N, Hossain MF, Rahman T. Diabetes mellitus: insights from epidemiology, biochemistry, risk factors, diagnosis, complications and comprehensive management. Diabetology. 2021;2(2):36-50.
Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 2012;27(4):269-273.
Khunti K. SGLT2 inhibitors in people with and without T2DM. Nat Rev Endocrinol. 2021;17(2):75-76.
Ikonomidis I, Pavlidis G, Thymis J, et al. Effects of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and their combination on endothelial glycocalyx, arterial function, and myocardial work index in patients with type 2 diabetes mellitus after 12-month treatment. J Am Heart Assoc. 2020;9(9):e015716.
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357.
Cannon CP, Pratley R, Dagogo-Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. 2020;383(15):1425-1435.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.
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):644-657.
Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424.
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
Thum T, Galuppo P, Wolf C, et al. microRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007;116(3):258-267.
Wojciechowska A, Braniewska A, Kozar-Kamińska K. microRNA in cardiovascular biology and disease. Adv Clin Exp Med. 2017;26(5):865-874.
Mao L, Liu S, Hu L, et al. miR-30 family: a promising regulator in development and disease. Biomed Res Int. 2018;2018:9623412.
Zhang X, Dong S, Jia Q, et al. The microRNA in ventricular remodeling: the miR-30 family. Biosci Rep. 2019;39(8):BSR20190788.
Zang J, Maxwell AP, Simpson DA, McKay GJ. Differential expression of urinary exosomal microRNAs miR-21-5p and miR-30b-5p in individuals with diabetic kidney disease. Sci Rep. 2019;9(1):10900.
Yang SJ, Yang SY, Wang DD, et al. The miR-30 family: versatile players in breast cancer. Tumour Biol. 2017;39(3):1010428317692204.
Chipman LB, Pasquinelli AE. miRNA targeting: growing beyond the seed. Trends Genet. 2019;35(3):215-222.
Lupsa BC, Inzucchi SE. Use of SGLT2 inhibitors in type 2 diabetes: weighing the risks and benefits. Diabetologia. 2018;61(10):2118-2125.
Henry RR, Thakkar P, Tong C, Polidori D, Alba M. Efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in patients with type 1 diabetes. Diabetes Care. 2015;38(12):2258-2265.
Chen S, Coronel R, Hollmann MW, Weber NC, Zuurbier CJ. Direct cardiac effects of SGLT2 inhibitors. Cardiovasc Diabetol. 2022;21(1):45.
Cinti F, Moffa S, Impronta F, et al. Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date. Drug Des Devel Ther. 2017;11:2905-2919.
Rodbard HW, Giaccari A, Lajara R, et al. Sotagliflozin added to optimized insulin therapy leads to HbA1c reduction without weight gain in adults with type 1 diabetes: a pooled analysis of inTandem1 and inTandem2. Diabetes Obes Metab. 2020;22(11):2089-2096.
Sands AT, Zambrowicz BP, Rosenstock J, et al. Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct therapy to insulin in type 1 diabetes. Diabetes Care. 2015;38(7):1181-1188.
Buse JB, Garg SK, Rosenstock J, et al. Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes: the North American inTandem1 study. Diabetes Care. 2018;41(9):1970-1980.
Garg SK, Henry RR, Banks P, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med. 2017;377(24):2337-2348.
Powell DR, Zambrowicz B, Morrow L, et al. Sotagliflozin decreases postprandial glucose and insulin concentrations by delaying intestinal glucose absorption. J Clin Endocrinol Metab. 2020;105(4):dgz258.
Danne T, Cariou B, Banks P, et al. HbA1c and hypoglycemia reductions at 24 and 52 weeks with sotagliflozin in combination with insulin in adults with type 1 diabetes: the European inTandem2 study. Diabetes Care. 2018;41(9):1981-1990.
Hsia DS, Grove O, Cefalu WT. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Curr Opin Endocrinol Diabetes Obes. 2017;24(1):73-79.
DeFronzo RA, Reeves WB, Awad AS. Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors. Nat Rev Nephrol. 2021;17(5):319-334.
Birkeland KI, Jørgensen ME, Carstensen B, et al. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis. Lancet Diabetes Endocrinol. 2017;5(9):709-717.
Marathe PH, Gao HX, Close KL. American diabetes association standards of medical care in diabetes 2017. J Diabetes. 2017;9(4):320-324.
Scheen AJ. Beneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: a common comorbidity associated with severe complications. Diabetes Metab. 2019;45(3):213-223.
Huang Y, Jiang Z, Wei Y. Efficacy and safety of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a meta-analysis of randomized controlled trials. Exp Ther Med. 2021;21(4):382.
Ferrannini E, Solini A. Therapy: SGLT inhibition in T1DM - definite benefit with manageable risk. Nat Rev Endocrinol. 2017;13(12):698-699.
Haidar A, Lovblom LE, Cardinez N, et al. Empagliflozin add-on therapy to closed-loop insulin delivery in type 1 diabetes: a 2 × 2 factorial randomized crossover trial. Nat Med. 2022;28(6):1269-1276.
Mathieu C, Van Den Mooter L, Eeckhout B. Empagliflozin in type 1 diabetes. Diabetes Metab Syndr Obes. 2019;12:1555-1561.
McCrimmon RJ, Henry RR. SGLT inhibitor adjunct therapy in type 1 diabetes. Diabetologia. 2018;61(10):2126-2133.
Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5(11):864-876.
Yang S, Liu Y, Zhang S, et al. Risk of diabetic ketoacidosis of SGLT2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials. Front Pharmacol. 2023;14:1145587.
Nuffer W, Williams B, Trujillo JM. A review of sotagliflozin for use in type 1 diabetes. Ther Adv Endocrinol Metab. 2019;10:2042018819890527.
Taylor SI, Blau JE, Rother KI, Beitelshees AL. SGLT2 inhibitors as adjunctive therapy for type 1 diabetes: balancing benefits and risks. Lancet Diabetes Endocrinol. 2019;7(12):949-958.
Jensen J, Omar M, Kistorp C, et al. Metabolic effects of empagliflozin in heart failure: a randomized, double-blind, and placebo-controlled trial (empire HF metabolic). Circulation. 2021;143(22):2208-2210.
Bailey CJ. Uric acid and the cardio-renal effects of SGLT2 inhibitors. Diabetes Obes Metab. 2019;21(6):1291-1298.
Esterline RL, Vaag A, Oscarsson J, Vora J. Mechanisms in endocrinology: SGLT2 inhibitors: clinical benefits by restoration of normal diurnal metabolism? Eur J Endocrinol. 2018;178(4):R113-R125.
Requena-Ibáñez JA, Santos-Gallego CG, Rodriguez-Cordero A, et al. Mechanistic insights of empagliflozin in nondiabetic patients with HFrEF: from the EMPA-TROPISM study. JACC Heart Fail. 2021;9(8):578-589.
Basu D, Huggins LA, Scerbo D, et al. Mechanism of increased LDL (low-density lipoprotein) and decreased triglycerides with SGLT2 (sodium-glucose cotransporter 2) inhibition. Arterioscler Thromb Vasc Biol. 2018;38(9):2207-2216.
Szekeres Z, Toth K, Szabados E. The effects of SGLT2 inhibitors on lipid metabolism. Metabolites. 2021;11(2):87.
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):508-511.
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.
Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care. 2016;39(7):1108-1114.
Lehrke M. SGLT2 inhibition: changing what fuels the heart. J Am Coll Cardiol. 2019;73(15):1945-1947.
Thomas MC, Cherney DZI. The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia. 2018;61(10):2098-2107.
Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol. 2019;73(15):1931-1944.
Santos-Gallego CG, Mayr M, Badimon J. SGLT2 inhibitors in heart failure: targeted metabolomics and energetic metabolism. Circulation. 2022;146(11):819-821.
Owen BM, Ding X, Morgan DA, et al. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. 2014;20(4):670-677.
Schork A, Saynisch J, Vosseler A, et al. Effect of SGLT2 inhibitors on body composition, fluid status and renin-angiotensin-aldosterone system in type 2 diabetes: a prospective study using bioimpedance spectroscopy. Cardiovasc Diabetol. 2019;18(1):46.
Avogaro A, Fadini GP, Del Prato S. Reinterpreting cardiorenal protection of renal sodium-glucose cotransporter 2 inhibitors via cellular life history programming. Diabetes Care. 2020;43(3):501-507.
Rangaswami J, Bhalla V, de Boer IH, et al. Cardiorenal protection with the newer antidiabetic agents in patients with diabetes and chronic kidney disease: a scientific statement from the American Heart Association [published correction appears in Circulation. 2020 Oct 27;142(17):e304] [published correction appears in Circulation. 2021 Jun;143(22):e1019-e1020]. Circulation. 2020;142(17):e265-e286.
Liu H, Sridhar VS, Boulet J, et al. Cardiorenal protection with SGLT2 inhibitors in patients with diabetes mellitus: from biomarkers to clinical outcomes in heart failure and diabetic kidney disease. Metabolism. 2022;126:154918.
Pérez MS, Rodríguez-Capitán J, Requena-Ibáñez JA, et al. Rationale and design of the SOTA-P-CARDIA trial (ATRU-V): sotagliflozin in HFpEF patients without diabetes. Cardiovasc Drugs Ther. 2023.
Affan M, Dar MS. Sotagliflozin: an insight into the first dual SGLT inhibitor now approved for heart failure. Ir J Med Sci. 2023;193.
Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021;384(2):117-128.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306.
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.
Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845-854.
Cassis P, Locatelli M, Cerullo D, et al. SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy. JCI Insight. 2018;3(15):e98720.
Wilcox CS. Antihypertensive and renal mechanisms of SGLT2 (sodium-glucose linked transporter 2) inhibitors. Hypertension. 2020;75(4):894-901.
Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors. J Am Coll Cardiol. 2020;75(4):422-434.
Sano M. Sodium glucose cotransporter (SGLT)-2 inhibitors alleviate the renal stress responsible for sympathetic activation. Ther Adv Cardiovasc Dis. 2020;14:1753944720939383.
Kaur A, Mackin ST, Schlosser K, et al. Systematic review of microRNA biomarkers in acute coronary syndrome and stable coronary artery disease. Cardiovasc Res. 2020;116(6):1113-1124.
Xiao J, Gao R, Bei Y, et al. Circulating miR-30d predicts survival in patients with acute heart failure. Cell Physiol Biochem. 2017;41(3):865-874.
Ellis KL, Cameron VA, Troughton RW, Frampton CM, Ellmers LJ, Richards AM. Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients. Eur J Heart Fail. 2013;15(10):1138-1147.
Li Y, Maegdefessel L. My heart will go on-beneficial effects of anti-MiR-30 after myocardial infarction. Ann Transl Med. 2016;4(7):144.
Shen Y, Shen Z, Miao L, et al. miRNA-30 family inhibition protects against cardiac ischemic injury by regulating cystathionine-γ-lyase expression. Antioxid Redox Signal. 2015;22(3):224-240.
Huang Y, Chen J, Zhou Y, et al. Circulating miR-30 is related to carotid artery atherosclerosis. Clin Exp Hypertens. 2016;38(5):489-494.
Yuan CT, Li XX, Cheng QJ, Wang YH, Wang JH, Liu CL. miR-30a regulates the atrial fibrillation-induced myocardial fibrosis by targeting snail 1. Int J Clin Exp Pathol. 2015;8(12):15527-15536.
Duisters RF, Tijsen AJ, Schroen B, et al. miR-133 and miR-30 regulate connective tissue growth factor. Circ Res. 2009;104(2):170-178.
Zhuo R, Fu S, Li S, et al. Desregulated microRNAs in aging-related heart failure. Front Genet. 2014;5:186.
Li J, Salvador AM, Li G, et al. miR-30d regulates cardiac remodeling by intracellular and paracrine signaling. Circ Res. 2021;128(1):e1-e23.
Roca-Alonso L, Castellano L, Mills A, et al. Myocardial miR-30 downregulation triggered by doxorubicin drives alterations in β-adrenergic signaling and enhances apoptosis. Cell Death Dis. 2015;6(5):e1754.
Kudulaiti N, Zhang H, Qiu T, et al. The relationship between IDH1 mutation status and metabolic imaging in nonenhancing supratentorial diffuse gliomas: a 11C-MET PET study. Mol Imaging. 2019;18:1536012119894087.
Rubiś P, Totoń-Żurańska J, Wiśniowska-Śmiałek S, et al. Relations between circulating microRNAs (miR-21, miR-26, miR-29, miR-30 and miR-133a), extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy. Int J Cardiol. 2017;231:201-206.
Morishima M, Iwata E, Nakada C, et al. Atrial fibrillation-mediated upregulation of miR-30d regulates myocardial electrical remodeling of the G-protein-gated K+ channel, IK.ACh. Circ J. 2016;80(6):1346-1355.
De Rosa S, Eposito F, Carella C, et al. Transcoronary concentration gradients of circulating microRNAs in heart failure. Eur J Heart Fail. 2018;20(6):1000-1010.
Maciejak A, Kostarska-Srokosz E, Gierlak W, et al. Circulating miR-30a-5p as a prognostic biomarker of left ventricular dysfunction after acute myocardial infarction. Sci Rep. 2018;8:9883.
Pan W, Zhong Y, Cheng C, et al. miR-30-regulated autophagy mediates angiotensin Ⅱ-induced myocardial hypertrophy. PLoS One. 2013;8(1):e53950.
Melman YF, Shah R, Danielson K, et al. Circulating microRNA-30d is associated with response to cardiac resynchronization therapy in heart failure and regulates cardiomyocyte apoptosis: a translational pilot study. Circulation. 2015;131(25):2202-2216.
Marfella R, Di Filippo C, Potenza N, et al. Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non-responders. Eur J Heart Fail. 2013;15(11):1277-1288.
Wu J, Zheng C, Fan Y, et al. Downregulation of microRNA-30 facilitates podocyte injury and is prevented by glucocorticoids. J Am Soc Nephrol. 2014;25(1):92-104.
Dieter C, Assmann TS, Costa AR, et al. miR-30e-5p and miR-15a-5p expressions in plasma and urine of type 1 diabetic patients with diabetic kidney disease. Front Genet. 2019;10:563.
Mahtal N, Lenoir O, Tinel C, Anglicheau D, Tharaux PL. microRNAs in kidney injury and disease. Nat Rev Nephrol. 2022;18(10):643-662.
Shi S, Yu L, Chiu C, et al. Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis. J Am Soc Nephrol. 2008;19(11):2159-2169.
Wei Q, Mi QS, Dong Z. The regulation and function of microRNAs in kidney diseases. IUBMB Life. 2013;65(7):602-614.
Wei Q, Bhatt K, He HZ, Mi QS, Haase VH, Dong Z. Targeted deletion of Dicer from proximal tubules protects against renal ischemia-reperfusion injury. J Am Soc Nephrol. 2010;21(5):756-761.
Gutiérrez-Escolano A, Santacruz-Vázquez E, Gómez-Pérez F. Dysregulated microRNAs involved in contrast-induced acute kidney injury in rat and human. Ren Fail. 2015;37(9):1498-1506.
Du B, Dai XM, Li S, et al. miR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5. Cell Death Dis. 2017;8(8):e2987.
Yuan XH, Li YW, Li P. miR-30c inhibits renal fibrosis in diabetic nephropathy by down-regulating ROCK2. Int J Clin Exp Med. 2020;13(8):5517-5526.
Lv W, Fan F, Wang Y, et al. Therapeutic potential of microRNAs for the treatment of renal fibrosis and CKD. Physiol Genom. 2018;50(1):20-34.
Zhang J, Zhang H, Liu J, et al. miR-30 inhibits TGF-β1-induced epithelial-to-mesenchymal transition in hepatocyte by targeting Snail1. Biochem Biophys Res Commun. 2012;417(3):1100-1105.
Liu L, Lin W, Zhang Q, Cao W, Liu Z. TGF-β induces miR-30d down-regulation and podocyte injury through Smad2/3 and HDAC3-associated transcriptional repression. J Mol Med (Berl). 2016;94(3):291-300.
Walton KL, Johnson KE, Harrison CA. Targeting TGF-β mediated SMAD signaling for the prevention of fibrosis. Front Pharmacol. 2017;8:461.
Ding H, Ye K, Triggle CR. Impact of currently used anti-diabetic drugs on myoendothelial communication. Curr Opin Pharmacol. 2019;45:1-7.
Li X, Römer G, Kerindongo RP, et al. Sodium glucose co-transporter 2 inhibitors ameliorate endothelium barrier dysfunction induced by cyclic stretch through inhibition of reactive oxygen species. Int J Mol Sci. 2021;22(11):6044.
Alshnbari AS, Millar SA, O'Sullivan SE, Idris I. Effect of sodium-glucose cotransporter-2 inhibitors on endothelial function: a systematic review of preclinical studies. Diabetes Ther. 2020;11(9):1947-1963.
Demolli S, Doebele C, Doddaballapur A, et al. microRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2. J Mol Cell Cardiol. 2015;88:111-119.
Fiedler U, Reiss Y, Scharpfenecker M, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-α and has a crucial role in the induction of inflammation. Nat Med. 2006;12(2):235-239.
Doebele C, Hergenreider E, Boon R, Reinfeld N, Zeiher AM, Dimmeler S. The miR-30 family is regulated by shear stress and affects the expression of inflammatory cell-cell adhesion molecules. Circulation. 2011;124:A15893.
Zhou Z, Chen Y, Zhang D, et al. microRNA-30-3p suppresses inflammatory factor-induced endothelial cell injury by targeting TCF21. Mediators Inflamm. 2019;2019:1342190.
Li G, Zong W, Liu L, Wu J, Pang J. Knockdown of long non-coding RNA plasmacytoma variant translocation 1 relieves ox-LDL-induced endothelial cell injury through regulating microRNA-30c-5p in atherosclerosis. Bioengineered. 2022;13(2):2791-2802.
Zhang T, Tian F, Wang J, Jing J, Zhou SS, Chen YD. Endothelial cell autophagy in atherosclerosis is regulated by miR-30-mediated translational control of ATG6. Cell Physiol Biochem. 2015;37(4):1369-1378.
Bi R, Dai Y, Ma Z, Zhang S, Wang L, Lin Q. Endothelial cell autophagy in chronic intermittent hypoxia is impaired by miRNA-30a-mediated translational control of Beclin-1. J Cell Biochem. 2019;120(3):4214-4224.
Zhang R, Xu J, Zhao J, Bai J. miR-30d suppresses cell proliferation of colon cancer cells by inhibiting cell autophagy and promoting cell apoptosis. Tumour Biol. 2017;39(6):1010428317703984.
Wang J, Jiao Y, Cui L, Jiang L. miR-30 functions as an oncomiR in gastric cancer cells through regulation of P53-mediated mitochondrial apoptotic pathway. Biosci Biotechnol Biochem. 2017;81(1):119-126.
Zong Y, Wu P, Nai C, et al. Effect of microRNA-30e on the behavior of vascular smooth muscle cells via targeting ubiquitin-conjugating enzyme E2I. Circ J. 2017;81(4):567-576.
Bae Y, Hwang JS, Shin YJ. miR-30c-1 encourages human corneal endothelial cells to regenerate through ameliorating senescence. Aging (Albany NY). 2021;13(7):9348-9372.
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.
Abdollahi E, Keyhanfar F, Delbandi AA, Falak R, Hajimiresmaiel SJ, Shafiei M. Dapagliflozin exerts anti-inflammatory effects via inhibition of LPS-induced TLR-4 overexpression and NF-κB activation in human endothelial cells and differentiated macrophages. Eur J Pharmacol. 2022;918:174715.
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;8:5276.
Nasiri-Ansari Ν, Dimitriadis GK, Agrogiannis G, et al. Canagliflozin attenuates the progression of atherosclerosis and inflammation process in APOE knockout mice. Cardiovasc Diabetol. 2018;17(1):106.
Ortega R, Collado A, Selles F, et al. SGLT-2 (sodium-glucose cotransporter 2) inhibition reduces ang Ⅱ (angiotensin Ⅱ)-induced dissecting abdominal aortic aneurysm in ApoE (apolipoprotein E) knockout mice. Arterioscler Thromb Vasc Biol. 2019;39(8):1614-1628.
Nakao M, Shimizu I, Katsuumi G, et al. Empagliflozin maintains capillarization and improves cardiac function in a murine model of left ventricular pressure overload. Sci Rep. 2021;11(1):18384.
Uthman L, Homayr A, Juni RP, et al. Empagliflozin and dapagliflozin reduce ROS generation and restore NO bioavailability in tumor necrosis factor α-stimulated human coronary arterial endothelial cells. Cell Physiol Biochem. 2019;53(5):865-886.
Vial G, Dubouchaud H, Couturier K, Lanson M, Leverve X, Demaison L. Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes. Mol Cell Biochem. 2008;310(1):93-102.
Santos-Gallego CG, Requena-Ibáñez JA, Picatoste B, et al. Cardioprotective effect of empagliflozin and circulating ketone bodies during acute myocardial infarction. Circ Cardiovasc Imaging. 2023;16(4):e015298.
Luo EF, Li HX, Qin YH, et al. Role of ferroptosis in the process of diabetes-induced endothelial dysfunction. World J Diabetes. 2021;12(2):124-137.
Ma S, He LL, Zhang GR, et al. Canagliflozin mitigates ferroptosis and ameliorates heart failure in rats with preserved ejection fraction. Naunyn-Schmiedebergs Arch Pharmacol. 2022;395(8):945-962.
Quagliariello V, De Laurentiis M, Rea D, et al. The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with doxorubicin. Cardiovasc Diabetol. 2021;20(1):150.
Jayasuriya R, Ganesan K, Xu B, Ramkumar KM. Emerging role of long non-coding RNAs in endothelial dysfunction and their molecular mechanisms. Biomed Pharmacother. 2022;145:112421.
Nemecz M, Alexandru N, Tanko G, Georgescu A. Role of microRNA in endothelial dysfunction and hypertension. Curr Hypertens Rep. 2016;18(12):87.
Zeng Q, Liu J. Silencing circ_0001879 inhibits the proliferation and migration of human retinal microvascular endothelial cells under high-glucose conditions via modulating miR-30-3p. Gene. 2020;760:144992.
Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling: concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35(3):569-582.
Berezin AE, Berezin AA. Adverse cardiac remodelling after acute myocardial infarction: old and new biomarkers. Dis Markers. 2020;2020:1215802.
Azevedo PS, Polegato BF, Minicucci MF, Paiva SAR, Zornoff LAM. Cardiac remodeling: concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment. Arq Bras Cardiol. 2016;106(1):62-69.
Burchfield JS, Xie M, Hill JA. Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation. 2013;128(4):388-400.
Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J Am Coll Cardiol. 2021;77(3):243-255.
Lee MMY, Brooksbank KJM, Wetherall K, et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation. 2021;143(6):516-525.
Omar M, Jensen J, Ali M, et al. Associations of empagliflozin with left ventricular volumes, mass, and function in patients with heart failure and reduced ejection fraction. JAMA Cardiol. 2021;6(7):836.
Mason T, Coelho-Filho OR, Verma S, et al. Empagliflozin reduces myocardial extracellular volume in patients with type 2 diabetes and coronary artery disease. JACC. 2021;14(6):1164-1173.
Verma S, Garg A, Yan AT, et al. Effect of empagliflozin on left ventricular mass and diastolic function in individuals with diabetes: an important clue to the EMPA-REG OUTCOME trial? Diabetes Care. 2016;39(12):e212-e213.
Harrington J, Udell JA, Jones WS, et al. Empagliflozin in patients post myocardial infarction rationale and design of the EMPACT-MI trial. Am Heart J. 2022;253:86-98.
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):7642-7659.
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):452-459.
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):543-553.
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.
Lin B, Koibuchi N, Hasegawa Y, et al. Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc Diabetol. 2014;13:148.
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.
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):2624-2635.
Jiang K, Xu Y, Wang D, et al. Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis. Protein Cell. 2022;13(5):336-359.
Engelhardt S, Hein L, Keller U, Klämbt K, Lohse MJ. Inhibition of Na+-H+ exchange prevents hypertrophy, fibrosis, and heart failure in beta(1)-adrenergic receptor transgenic mice. Circ Res. 2002;90(7):814-819.
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):722-726.
Chung YJ, Park KC, Tokar S, et al. Off-target effects of sodium-glucose co-transporter 2 blockers: empagliflozin does not inhibit Na+/H+ exchanger-1 or lower[Na+]i in the heart. Cardiovasc Res. 2021;117(14):2794-2806.
Cappetta D, De Angelis A, Ciuffreda LP, et al. Amelioration of diastolic dysfunction by dapagliflozin in a non-diabetic model involves coronary endothelium. Pharmacol Res. 2020;157:104781.
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):119-132.
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.
Song Y, Huang C, Sin J, et al. Attenuation of adverse postinfarction left ventricular remodeling with empagliflozin enhances mitochondria-linked cellular energetics and mitochondrial biogenesis. Int J Mol Sci. 2021;23(1):437.
Reddy S, Zhao M, Hu DQ, et al. Dynamic microRNA expression during the transition from right ventricular hypertrophy to failure. Physiol Genomics. 2012;44(10):562-575.
Bao J, Lu Y, She Q, et al. microRNA-30 regulates left ventricular hypertrophy in chronic kidney disease. JCI Insight. 2021;6(10):138027.
Li J, Sha Z, Zhu X, et al. Targeting miR-30d reverses pathological cardiac hypertrophy. EBioMedicine. 2022;81:104108.
Duan Q, Chen C, Yang L, et al. microRNA regulation of unfolded protein response transcription factor XBP1 in the progression of cardiac hypertrophy and heart failure in vivo. J Transl Med. 2015;13:363.
Margariti A, Li H, Chen T, et al. XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation. J Biol Chem. 2013;288(2):859-872.
Forini F, Kusmic C, Nicolini G, et al. Triiodothyronine prevents cardiac ischemia/reperfusion mitochondrial impairment and cell loss by regulating miR30a/p53 axis. Endocrinology. 2014;155(11):4581-4590.
Li J, Donath S, Li Y, Qin D, Prabhakar BS, Li P. miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway. PLoS Genet. 2010;6(1):e1000795.
Cokkinos DV, Chryssanthopoulos S. Thyroid hormones and cardiac remodeling. Heart Fail Rev. 2016;21(4):365-372.
Yin Y, Yang C. miRNA-30-3p improves myocardial ischemia via the PTEN/PI3K/AKT signaling pathway. J Cell Biochem. 2019;120(10):17326-17336.
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