{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:55:52Z","timestamp":1790697352472,"version":"4.1.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T00:00:00Z","timestamp":1542758400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"DOI":"10.3389\/fphys.2018.01575","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T09:00:35Z","timestamp":1542790835000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":174,"title":["Direct Cardiac Actions of Sodium Glucose Cotransporter 2 Inhibitors Target Pathogenic Mechanisms Underlying Heart Failure in Diabetic Patients"],"prefix":"10.3389","volume":"9","author":[{"given":"Laween","family":"Uthman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius","family":"Baartscheer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cees A.","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan W. T.","family":"Fiolet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius C.","family":"Kuschma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus W.","family":"Hollmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Coronel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina C.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coert J.","family":"Zuurbier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,11,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.01077","article-title":"Empagliflozin limits myocardial infarction in vivo and cell death in vitro: role of STAT3, mitochondria, and redox aspects.","volume":"8","author":"Andreadou","year":"2017","journal-title":"Front. Physiol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010091","article-title":"Inflammation determines the pro-adhesive properties of high extracellular D-glucose in human endothelial cells in vitro and rat microvessels in vivo.","volume":"5","author":"Azcutia","year":"2010","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1038\/bjp.2008.189","article-title":"Chronic inhibition of the Na+\/H+-exchanger causes regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling.","volume":"154","author":"Baartscheer","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/S0008-6363(02)00848-9","article-title":"[Na+]I and the driving force of the Na+\/Ca2+-exchanger in heart.","volume":"57","author":"Baartscheer","year":"","journal-title":"Cardiovasc. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/S0008-6363(02)00809-X","article-title":"Increased Na+\/H+-exchange activity is the cause of increased [Na+]I and underlies disturbed calcium handling in the rabbit pressure and volume overload heart failure model.","volume":"57","author":"Baartscheer","year":"","journal-title":"Heart Fail."},{"key":"B6","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0008-6363(02)00854-4","article-title":"S R calcium handling and calcium after-transients in a rabbit model of heart failure.","volume":"58","author":"Baartscheer","year":"","journal-title":"Heart Fail."},{"key":"B7","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.cardiores.2004.09.024","article-title":"Chronic inhibition of Na+\/H+-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure.","volume":"65","author":"Baartscheer","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1007\/s00125-016-4134-x","article-title":"Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+\/H+ exchanger in rats and rabbits.","volume":"60","author":"Baartscheer","year":"2017","journal-title":"Diabetologia"},{"key":"B9","doi-asserted-by":"publisher","first-page":"229","DOI":"10.2174\/187152508785909546","article-title":"Sodium ion transporters as new therapeutic targets in heart failure.","volume":"6","author":"Baartscheer","year":"2008","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/cvr\/cvp190","article-title":"SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states.","volume":"84","author":"Banerjee","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.yjmcc.2013.05.010","article-title":"Intracellular Na+ and cardiac metabolism.","volume":"61","author":"Bay","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1093\/cvr\/cvr034","article-title":"AMPK activation, a preventive therapeutic target in the transition from cardiac injury to heart failure.","volume":"90","author":"Beauloye","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1016\/S0735-1097(02)02160-5","article-title":"Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with 31P-SLOOP magnetic resonance spectroscopy.","volume":"40","author":"Beer","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1146\/annurev-physiol-020911-153308","article-title":"Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction.","volume":"76","author":"Bers","year":"2014","journal-title":"Annu. Rev. Physiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1161\/CIRCRESAHA.118.310082","article-title":"Calcium signaling and reactive oxygen species in Mitochondria.","volume":"122","author":"Bertero","year":"2018","journal-title":"Circ. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.2337\/db07-0481.Additional","article-title":"Mitochondrial energetics in the heart in obesity-related.","volume":"56","author":"Boudina","year":"2007","journal-title":"Diabetes"},{"key":"B17","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1007\/s00125-014-3171-6","article-title":"Molecular mechanisms of diabetic cardiomyopathy.","volume":"57","author":"Bugger","year":"2014","journal-title":"Diabetologia"},{"key":"B18","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jacbts.2017.07.003","article-title":"Empagliflozin prevents worsening of cardiac function in an experimental model of pressure overload-induced heart failure.","volume":"2","author":"Byrne","year":"2017","journal-title":"JACC Basic Transl. Sci."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-015-0187-2","article-title":"Cardiac structure and function are altered in type 2 diabetes and Non-alcoholic fatty liver disease and associate with glycemic control.","volume":"14","author":"Cassidy","year":"2015","journal-title":"Cardiovasc. Diabetol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1161\/CIRCULATIONAHA.114.014796","article-title":"Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the reduction of atherothrombosis for continued health (REACH) registry.","volume":"132","author":"Cavender","year":"2015","journal-title":"Circulation"},{"key":"B21","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1002\/dmrr.689","article-title":"Role of endothelin-1, sodium hydrogen exchanger-1 and mitogen activated protein kinase (MAPK) activation in glucose-induced cardiomyocyte hypertrophy.","volume":"23","author":"Chen","year":"2007","journal-title":"Diabetes Metab. Res. Rev."},{"key":"B22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.tem.2017.10.009","article-title":"AMP-activated protein kinase regulation of the NLRP3 inflammasome during aging.","volume":"29","author":"Cordero","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.1016\/j.bbadis.2013.04.002","article-title":"Electrophysiological changes in heart failure and their implications for arrhythmogenesis.","volume":"1832","author":"Coronel","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B24","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1177\/1479164112471064","article-title":"Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology.","volume":"10","author":"Cubbon","year":"2013","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/aps.2012.155","article-title":"Amiloride attenuates lipopolysaccharide-accelerated atherosclerosis via inhibition of NHE1-dependent endothelial cell apoptosis.","volume":"34","author":"Cui","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1007\/s00125-007-0628-x","article-title":"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.","volume":"50","author":"Darmellah","year":"2007","journal-title":"Diabetologia"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01303","article-title":"Myocyte [Na+]I dysregulation in heart failure and diabetic cardiomyopathy.","volume":"9","author":"Despa","year":"2018","journal-title":"Front. Physiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.1161\/01.CIR.0000016701.85760.97","article-title":"Intracellular Na+ concentration is elevated in heart failure but Na\/K pump function is unchanged.","volume":"105","author":"Despa","year":"2002","journal-title":"Circulation"},{"key":"B29","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1093\/cvr\/cvs213","article-title":"Na+\/K+-ATPase 2-isoform preferentially modulates Ca2+ transients and sarcoplasmic reticulum Ca2+ release in cardiac myocytes.","volume":"95","author":"Despa","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1161\/CIRCRESAHA.118.312708","article-title":"Mitochondrial ROS drive sudden cardiac death and chronic proteome remodeling in heart failurenovelty and significance.","volume":"123","author":"Dey","year":"2018","journal-title":"Circ. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.ijcard.2017.05.032","article-title":"Sodium-dependent glucose transporters (SGLT) in human ischemic heart: a new potential pharmacological target.","volume":"243","author":"Di Franco","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128870","article-title":"Elevated sodium and dehydration stimulate inflammatory signaling in endothelial cells and promote atherosclerosis.","volume":"10","author":"Dmitrieva","year":"2015","journal-title":"PLoS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/S2213-8587(15)00121-7","article-title":"Effect of metformin pretreatment on myocardial injury during coronary artery bypass surgery in patients without diabetes (MetCAB): a double-blind, randomised controlled trial.","volume":"3","author":"El Messaoudi","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.vph.2018.06.006","article-title":"Hyperglycaemic impairment of PAR2-mediated vasodilation: prevention by inhibition of aortic endothelial sodium-glucose-co- Transporter-2 and minimizing oxidative stress.","volume":"109","author":"El-daly","year":"2018","journal-title":"Vascul. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1161\/01.RES.0000014966.97486.C0","article-title":"Inhibition of Na+-H+ exchange prevents hypertrophy, fibrosis, and heart failure in beta1-adrenergic receptor transgenic mice.","volume":"90","author":"Engelhardt","year":"2002","journal-title":"Circ. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/nature12537.Diabetic","article-title":"Diabetic hyperglycemia activates CaMKII and arrhythmias by O linked glycosylation.","volume":"502","author":"Erickson","year":"2013","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/sj\/jhh\/1001342","article-title":"Salt intake and hypertension therapy.","volume":"16","author":"Feldstein","year":"2002","journal-title":"J. Hum. Hypertens."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.2337\/dc15-0355","article-title":"Energy balance after sodium\u2013glucose cotransporter 2 inhibition.","volume":"38","author":"Ferrannini","year":"2015","journal-title":"Diabetes Care"},{"key":"B39","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","article-title":"Metformin: from mechanisms of action to therapies.","volume":"20","author":"Foretz","year":"2014","journal-title":"Cell Metab."},{"key":"B40","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1093\/cvr\/cvx011","article-title":"An overview of the inflammatory signalling mechanisms in themyocardiumunderlying the development of diabetic cardiomyopathy.","volume":"113","author":"Frati","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1093\/cvr\/cvs116","article-title":"Calcium-mediated cell death during myocardial reperfusion.","volume":"94","author":"Garcia-Dorado","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1177\/1479164117733626","article-title":"Dapagliflozin attenuates human vascular endothelial cell activation and induces vasorelaxation: a potential mechanism for inhibition of atherogenesis.","volume":"15","author":"Gaspari","year":"2017","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02795-4","article-title":"AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation.","volume":"9","author":"G\u00e9linas","year":"2018","journal-title":"Nat. Commun."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2959","DOI":"10.1021\/bi2018909","article-title":"Role of mitochondrial Ca2+ in the regulation of cellular energetics.","volume":"51","author":"Glancy","year":"2012","journal-title":"Biochemistry"},{"key":"B45","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s11010-014-2262-5","article-title":"Dapagliflozin reduces the amplitude of shortening and Ca2+ transient in ventricular myocytes from streptozotocin-induced diabetic rats.","volume":"400","author":"Hamouda","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"L1027","DOI":"10.1152\/ajplung.00167.2015","article-title":"SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery.","volume":"309","author":"Han","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.2337\/db16-0058","article-title":"The Na+\/glucose cotransporter inhibitor canagliflozin activates AMPK by inhibiting mitochondrial function and increasing cellular AMP levels.","volume":"65","author":"Hawley","year":"2016","journal-title":"Diabetes Metab. Res. Rev."},{"key":"B48","doi-asserted-by":"publisher","first-page":"4285","DOI":"10.2337\/db15-0107","article-title":"AMPK suppresses vascular inflammation in vivo by inhibiting signal transducer and activator of transcription-1.","volume":"64","author":"He","year":"2015","journal-title":"Diabetes Metab. Res. Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41569-018-0004-1","article-title":"Role of salt intake in prevention of cardiovascular disease: controversies and challenges.","volume":"15","author":"He","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1093\/cvr\/cvn301","article-title":"Energy metabolism in heart failure and remodelling.","volume":"81","author":"Ingwall","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1046\/j.1540-8167.2001.00496.x","article-title":"Arrhythmogenesis in heart failure.","volume":"12","author":"Janse","year":"2001","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2","DOI":"10.4172\/2329-6607.1000210","article-title":"Sodium glucose transporter 2 (SGLT2) inhibition does not protect the myocardium from acute ischemic reperfusion injury but modulates post- ischemic mitochondrial function.","volume":"6","author":"Jespersen","year":"2017","journal-title":"Cardiovasc. Pharmacol. Open Access."},{"key":"B53","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1161\/CIRCRESAHA.117.311586","article-title":"Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity.","volume":"122","author":"Jia","year":"2018","journal-title":"Circ. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s11010-013-1861-x","article-title":"Conundrum of pathogenesis of diabetic cardiomyopathy: role of vascular endothelial dysfunction, reactive oxygen species, and mitochondria.","volume":"386","author":"Joshi","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0002-9149(74)90089-7","article-title":"Role of diabetes in congestive heart failure: the Framingham study.","volume":"34","author":"Kannel","year":"1974","journal-title":"Am. J. Cardiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.yjmcc.2013.02.006","article-title":"NHE-1: still a viable therapeutic target.","volume":"61","author":"Karmazyn","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130605","article-title":"Expression of SGLT1 in human hearts and impairment of cardiac glucose uptake by phlorizin during ischemia-reperfusion injury in mice.","volume":"10","author":"Kashiwagi","year":"2015","journal-title":"PLoS One"},{"key":"B58","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1111\/j.1463-1326.2011.01397.x","article-title":"Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects.","volume":"13","author":"Kasichayanula","year":"2011","journal-title":"Diabetes Obes. Metab."},{"key":"B59","doi-asserted-by":"publisher","first-page":"H738","DOI":"10.1152\/ajpheart.2001.280.2.H738","article-title":"Na+\/H+ exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats.","volume":"280","author":"Kusumoto","year":"2001","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1161\/JAHA.115.002183","article-title":"Intracellular Na+ concentration ([Na+]I) is elevated in diabetic hearts due to enhanced Na+-glucose cotransport.","volume":"4","author":"Lambert","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1713837115","article-title":"High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism.","volume":"115","author":"Lanaspa","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B62","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrcardio.2010.123","article-title":"Salt, aldosterone, and insulin resistance: impact on the cardiovascular system.","volume":"7","author":"Lastra","year":"2010","journal-title":"Nat. Rev. Cardiol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.freeradbiomed.2017.01.035","article-title":"Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts.","volume":"104","author":"Lee","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"3461","DOI":"10.1093\/eurheartj\/ehv442","article-title":"Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus.","volume":"37","author":"Levelt","year":"2016","journal-title":"Eur. Heart J."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12659\/MSMBR.907775","article-title":"Phlorizin exerts direct protective effects on palmitic acid (PA)-induced endothelial dysfunction by activating the PI3K\/AKT\/eNOS signaling pathway and increasing the levels of nitric oxide (NO).","volume":"24","author":"Li","year":"2018","journal-title":"Med. Sci. Monit. Basic Res."},{"key":"B66","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.yjmcc.2015.07.010","article-title":"Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission and alleviates endoplasmic reticulum stress-associated endothelial dysfunction.","volume":"86","author":"Li","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1161\/CIRCRESAHA.108.175919","article-title":"Enhancing mitochondrial Ca2+ uptake in myocytes from failing hearts restores energy supply and demand matching.","volume":"103","author":"Liu","year":"2008","journal-title":"Circ. Res."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1172\/JCI65268","article-title":"Diabetes increases mortality after myocardial infarction by oxidizing CaMKII.","volume":"123","author":"Luo","year":"2013","journal-title":"J. Clin. Invest."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23420-4","article-title":"Canagliflozin inhibits interleukin-1\u03b2-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms.","volume":"8","author":"Mancini","year":"2018","journal-title":"Sci. Rep."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/j.athoracsur.2007.10.054","article-title":"Sodium-hydrogen exchange inhibition by cariporide to reduce the risk of ischemic cardiac events in patients undergoing coronary artery bypass grafting: results of the EXPEDITION study.","volume":"85","author":"Mentzer","year":"2008","journal-title":"Ann. Thorac. Surg."},{"key":"B71","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s10741-012-9313-3","article-title":"Diabetic cardiomyopathy: pathophysiology and clinical features.","volume":"18","author":"Miki","year":"2013","journal-title":"Heart Fail. Rev."},{"key":"B72","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ijcard.2015.08.111","article-title":"Type-2 diabetes increases autophagy in the human heart through promotion of Beclin-1 mediated pathway.","volume":"202","author":"Munasinghe","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/j.immuni.2013.05.016","article-title":"K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter.","volume":"38","author":"Mu\u00f1oz-Planillo","year":"2013","journal-title":"Immunity"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1093\/eurheartj\/ehv305","article-title":"Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications.","volume":"36","author":"M\u00fcnzel","year":"2015","journal-title":"Eur. Heart J."},{"key":"B75","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1161\/CIRCRESAHA.108.189050","article-title":"Regulation of intracellular and mitochondrial sodium in health and disease.","volume":"104","author":"Murphy","year":"2009","journal-title":"Circ. Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1002\/ehf2.12336","article-title":"Empagliflozin reduces Ca\/calmodulin-dependent kinase II activity in isolated ventricular cardiomyocytes.","volume":"5","author":"Mustroph","year":"2018","journal-title":"ESC Hear. Fail."},{"key":"B77","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes.","volume":"377","author":"Neal","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1161\/CIRCRESAHA.109.203836","article-title":"CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation.","volume":"106","author":"Neef","year":"2010","journal-title":"Circ. Res."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1056\/NEJMra063052","article-title":"The failing heart \u2014 an engine out of fuel.","volume":"356","author":"Neubauer","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112394","article-title":"The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity.","volume":"9","author":"Oelze","year":"2014","journal-title":"PLoS One"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1161\/CIRCULATIONAHA.117.030418","article-title":"Activation and inhibition of sodium-hydrogen exchanger is a mechanism that links the pathophysiology and treatment of diabetes mellitus with that of heart failure.","volume":"136","author":"Packer","year":"2017","journal-title":"Circulation"},{"key":"B82","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jacc.2013.02.092","article-title":"A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.","volume":"62","author":"Paulus","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/S0008-6363(02)00735-6","article-title":"Intracellular Na in animal models of hypertrophy and heart failure: contractile function and arrhythmogenesis.","volume":"57","author":"Pogwizd","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1161\/CIRCRESAHA.116.306206","article-title":"Insulin signaling and heart failure.","volume":"118","author":"Riehle","year":"2016","journal-title":"Circ. Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.vph.2012.11.004","article-title":"Na+\/H+ exchanger inhibitor induces vasorelaxation through nitric oxide production in endothelial cells via intracellular acidification-associated Ca2+ mobilization.","volume":"58","author":"Sasahara","year":"2013","journal-title":"Vascul. Pharmacol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1517\/17425255.2014.873788","article-title":"Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations.","volume":"10","author":"Scheen","year":"2014","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1016\/j.bbadis.2013.08.006","article-title":"Endothelial dysfunction - A major mediator of diabetic vascular disease.","volume":"1832","author":"Sena","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1161\/CIRCRESAHA.116.306923.Molecular","article-title":"Molecular and cellular mechanisms of cardiovascular disorders in diabetes.","volume":"118","author":"Shah","year":"2017","journal-title":"Circ. Res."},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00114","article-title":"Oxidative stress and NLRP3-inflammasome activity as significant drivers of diabetic cardiovascular complications: therapeutic implications.","volume":"9","author":"Sharma","year":"2018","journal-title":"Front. Physiol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.redox.2017.06.009","article-title":"The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats.","volume":"13","author":"Steven","year":"2017","journal-title":"Redox Biol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1124\/jpet.112.191593","article-title":"Tofogliflozin, a potent and highly specific sodium\/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice.","volume":"341","author":"Suzuki","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B92","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1530\/JOE-17-0457","article-title":"Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury.","volume":"236","author":"Tanajak","year":"2018","journal-title":"J. Endocrinol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1023\/A:1024985931797","article-title":"Na+ overload during ischemia and reperfusion in rat hearts: comparison of the Na+\/H+ exchange blockers EIPA, cariporide and eniporide.","volume":"250","author":"ten Hove","year":"2003","journal-title":"Mol. Cell. Biochem."},{"key":"B94","doi-asserted-by":"publisher","first-page":"3032","DOI":"10.1161\/01.CIR.102.25.3032","article-title":"Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations. main results of the GUARDIAN trial.","volume":"102","author":"Th\u00e9roux","year":"2000","journal-title":"Circulation"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1161\/hc4001.097183","article-title":"Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy.","volume":"104","author":"Tian","year":"2001","journal-title":"Circulation"},{"key":"B96","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1007\/s00125-017-4509-7","article-title":"Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+\/H+ exchanger, lowering of cytosolic Na+ and vasodilation.","volume":"61","author":"Uthman","year":"","journal-title":"Diabetologia"},{"key":"B97","article-title":"Administration of SGLT2 inhibitor empagliflozin against TNF-\u03b1 induced endothelial dysfunction in human venous and arterial endothelial cells.","volume":"32","author":"Uthman","year":"","journal-title":"FASEB J."},{"key":"B98","article-title":"Empagliflozin effects on ischemic contracture and I\/R injury in isolated mouse hearts perfused with or without insulin.","volume":"32","author":"Uthman","year":"","journal-title":"FASEB J."},{"key":"B99","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1161\/CIRCULATIONAHA.107.728550","article-title":"Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension.","volume":"117","author":"Van Heerebeek","year":"2008","journal-title":"Circulation"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/srep41166","article-title":"Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart.","volume":"7","author":"Van Steenbergen","year":"2017","journal-title":"Sci. Rep."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1016\/j.bbadis.2017.10.035","article-title":"Molecular mechanisms of cardiac pathology in diabetes \u2013 Experimental insights.","volume":"1864","author":"Varma","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"B102","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1046\/j.1471-4159.1996.67062379.x","article-title":"Protective effects of extracellular acidosis and blockade of sodium\/hydrogen ion exchange during recovery from metabolic inhibition in neuronal tissue culture.","volume":"67","author":"Vornov","year":"1996","journal-title":"J. Neurochem."},{"key":"B103","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1007\/s00424-014-1619-7","article-title":"Localizations of Na+-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart.","volume":"467","author":"Vrhovac","year":"2015","journal-title":"Pflugers Arch. Eur. J. Physiol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1017\/S0007114517002926","article-title":"Involvement of NLRP3 inflammasome in the impacts of sodium and potassium on insulin resistance in normotensive Asians.","volume":"119","author":"Wan","year":"2018","journal-title":"Br. J. Nutr."},{"key":"B105","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1093\/cvr\/cvn179","article-title":"Na+\/H+ exchanger is required for hyperglycaemia- induced endothelial dysfunction via calcium-dependent calpain.","volume":"80","author":"Wang","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"B106","year":"2012","journal-title":"Guideline: Sodium Intake for Adults and Children"},{"key":"B107","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s10557-017-6725-2","article-title":"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.","volume":"31","author":"Ye","year":"2017","journal-title":"Cardiovasc. Drugs Ther."},{"key":"B108","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/S0735-1097(00)00730-0","article-title":"Sarcolemmal Na+\/H+ exchanger activity and expression in human ventricular myocardium.","volume":"36","author":"Yokoyama","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"E1644","DOI":"10.1016\/S0735-1097(01)01608-4","article-title":"The Na+\/H+ exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction11This manuscript is dedicated to the memory of Karl-Ludwig Neuhaus (1944\u20132000).","volume":"38","author":"Zeymer","year":"2001","journal-title":"J. Am. Coll. Cardiol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.redox.2017.12.019","article-title":"Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission.","volume":"15","author":"Zhou","year":"2018","journal-title":"Redox Biol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/jcb.10631","article-title":"Human cardiomyocytes express high level of Na+\/glucose cotransporter 1 (SGLT1).","volume":"90","author":"Zhou","year":"2003","journal-title":"J. Cell. Biochem."},{"key":"B112","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.","volume":"373","author":"Zinman","year":"2015","journal-title":"N. Engl. J. Med."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphys.2018.01575\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T09:00:38Z","timestamp":1542790838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphys.2018.01575\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,21]]},"references-count":112,"alternative-id":["10.3389\/fphys.2018.01575"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2018.01575","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734515169.793575563","asserted-by":"object"}]},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,21]]},"article-number":"1575"}}