40 results match your criteria cardiomyocytes empagliflozin

Sodium-Glucose CoTransporter-2 Inhibitor Empagliflozin Ameliorates Sunitinib-Induced Cardiac Dysfunction via Regulation of AMPK-mTOR Signaling Pathway-Mediated Autophagy.

Front Pharmacol 2021 29;12:664181. Epub 2021 Apr 29.

Department of Cardiology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to decrease the adverse cardiac events and risks of cardiovascular mortality among patients with or without diabetes, which has made these drugs promising treatment options for patients with chronic heart failure. Cardiac dysfunction is a common and severe side effect induced by cancer chemotherapies, which seriously affects the prognosis and life quality of tumor patients. However, it is not clear whether SGLT2 inhibitors have cardiovascular benefits in patients with cancer chemotherapy-related cardiac dysfunction. Read More

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Reversing endothelial dysfunction with empagliflozin to improve cardiomyocyte function in cardiorenal syndrome.

Kidney Int 2021 05;99(5):1062-1064

Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France; Centre de Néphrologie et Transplantation Rénale, AP-HM, Hôpital de la Conception, Marseille, France.

Sodium-glucose cotransporter 2 inhibitors offer cardiovascular and renal benefits in patients with chronic kidney disease through not yet clearly defined mechanisms. Juni et al. showed that sodium-glucose cotransporter 2 inhibitor empagliflozin exposure in vitro can restore cardiomyocyte function by counteracting harmful effects of uremic serum on the endothelium-cardiomyocyte crosstalk between endothelial cells and cardiomyocytes. Read More

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Empagliflozin Disrupts a Tnfrsf12a-Mediated Feed Forward Loop That Promotes Left Ventricular Hypertrophy.

Cardiovasc Drugs Ther 2021 Apr 22. Epub 2021 Apr 22.

Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, Toronto, Ontario, M5B 1T8, Canada.

Purpose: Although the cardioprotective benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors are now widely appreciated, the mechanisms underlying these benefits remain unresolved. Tumor necrosis factor receptor superfamily member 12a (Tnfrsf12a) is a receptor for tumor necrosis factor superfamily member 12 (Tnfsf12). Tnfrsf12a is highly inducible and plays a key role in the development of cardiac hypertrophy and heart failure. Read More

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Cardiac Late Sodium Channel Current Is a Molecular Target for the Sodium/Glucose Cotransporter 2 Inhibitor Empagliflozin.

Circulation 2021 Jun 9;143(22):2188-2204. Epub 2021 Apr 9.

Alberta Diabetes Institute (K.P., M.F., W.L., A.B., J.S., J.W., T.P., C.S., J.M.S., P.E.L.), University of Alberta, Edmonton, Canada.xs.

Background: SGLT2 (sodium/glucose cotransporter 2) inhibitors exert robust cardioprotective effects against heart failure in patients with diabetes, and there is intense interest to identify the underlying molecular mechanisms that afford this protection. Because the induction of the late component of the cardiac sodium channel current (late-) is involved in the etiology of heart failure, we investigated whether these drugs inhibit late-.

Methods: Electrophysiological, in silico molecular docking, molecular, calcium imaging, and whole heart perfusion techniques were used to address this question. Read More

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Direct Cardiac Actions of the Sodium Glucose Co-Transporter 2 Inhibitor Empagliflozin Improve Myocardial Oxidative Phosphorylation and Attenuate Pressure-Overload Heart Failure.

J Am Heart Assoc 2021 Mar 13;10(6):e018298. Epub 2021 Mar 13.

Department of Physiology and Biophysics Mississippi Center for Obesity ResearchMississippi Center for Heart ResearchUniversity of Mississippi Medical Center Jackson MS.

Background We determined if the sodium glucose co-transporter 2 inhibitor empagliflozin attenuates pressure overload-induced heart failure in non-diabetic mellitus mice by direct cardiac effects and the mechanisms involved. Methods and Results Male C57BL/6J mice (4-6 months of age) were subjected to sham surgeries or transverse aortic constriction to produce cardiac pressure overload. Two weeks after transverse aortic constriction, empagliflozin (10 mg/kg per day) or vehicle was administered daily for 4 weeks. Read More

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Empagliflozin prevents from early cardiac injury post myocardial infarction in non-diabetic mice.

Eur J Pharm Sci 2021 Jun 6;161:105788. Epub 2021 Mar 6.

Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. Electronic address:

Objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been confirmed to reduce the rate of rehospitalization for heart failure and cardiovascular death in diabetic patients. The aim of our study was to investigate the cardioprotective role of SGLT2 inhibitors in early myocardial infarction (MI) of non-diabetic mice.

Methods: C57BL/6 mice underwent left artery coronary artery descending (LAD) ligation to induce MI. Read More

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Metabolic Aspects of Anthracycline Cardiotoxicity.

Curr Treat Options Oncol 2021 Feb 5;22(2):18. Epub 2021 Feb 5.

Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Via Nizza 52, 10126, Torino, Italy.

Opinion Statement: Heart failure (HF) is increasingly recognized as the major complication of chemotherapy regimens. Despite the development of modern targeted therapies such as monoclonal antibodies, doxorubicin (DOXO), one of the most cardiotoxic anticancer agents, still remains the treatment of choice for several solid and hematological tumors. The insurgence of cardiotoxicity represents the major limitation to the clinical use of this potent anticancer drug. Read More

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February 2021

Empagliflozin alleviates ethanol-induced cardiomyocyte injury through inhibition of mitochondrial apoptosis via a SIRT1/PTEN/Akt pathway.

Clin Exp Pharmacol Physiol 2021 Jun 1;48(6):837-845. Epub 2021 Feb 1.

Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Ethanol-induced myocardial injury involves multiple pathophysiological processes including apoptosis. Empagliflozin (EMPA), is a novel hypoglycaemic drug which possesses multiple pharmacologically relevant protective effects, including anti-apoptotic, anti-inflammatory and antioxidant effects. However, whether EMPA treatment has a protective effect on ethanol-induced myocardial injury has not been assessed, to the best of our knowledge. Read More

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Empagliflozin and Liraglutide Differentially Modulate Cardiac Metabolism in Diabetic Cardiomyopathy in Rats.

Int J Mol Sci 2021 Jan 25;22(3). Epub 2021 Jan 25.

Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are antihyperglycemic agents with cardioprotective properties against diabetic cardiomyopathy (DCM). However, the distinctive mechanisms underlying GLP-1RAs and SGLT2is in DCM are not fully elucidated. The purpose of this study was to investigate the impacts of GLP1RAs and/or SGLT2is on myocardial energy metabolism, cardiac function, and apoptosis signaling in DCM. Read More

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January 2021

Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis.

Protein Cell 2021 Jan 8. Epub 2021 Jan 8.

Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. Read More

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January 2021

Empagliflozin restores chronic kidney disease-induced impairment of endothelial regulation of cardiomyocyte relaxation and contraction.

Kidney Int 2021 05 23;99(5):1088-1101. Epub 2020 Dec 23.

Department of Physiology, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. Electronic address:

Chronic kidney disease (CKD) promotes development of cardiac abnormalities and is highly prevalent in patients with heart failure, particularly in those with preserved ejection fraction. CKD is associated with endothelial dysfunction, however, whether CKD can induce impairment of endothelium-to-cardiomyocyte crosstalk leading to impairment of cardiomyocyte function is not known. The sodium-glucose co-transporter 2 inhibitor, empagliflozin, reduced cardiovascular events in diabetic patients with or without CKD, suggesting its potential as a new treatment for heart failure with preserved ejection fraction. Read More

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Off-target effects of SGLT2 blockers: empagliflozin does not inhibit Na+/H+ exchanger-1 or lower [Na+]i in the heart.

Cardiovasc Res 2020 Nov 2. Epub 2020 Nov 2.

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom.

Aims: Empagliflozin (EMPA) is a potent inhibitor of the renal sodium-glucose cotransporter 2 (SGLT2) and an effective treatment for type-2 diabetes. In patients with diabetes and heart failure, EMPA has cardioprotective effects independent of improved glycaemic control, despite SGLT2 not being expressed in the heart. A number of non-canonical mechanisms have been proposed to explain these cardiac effects, most notably an inhibitory action on cardiac Na+/H+ exchanger 1 (NHE1), causing a reduction in intracellular [Na+] ([Na+]i). Read More

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November 2020

Empagliflozin Ameliorates Diastolic Dysfunction and Left Ventricular Fibrosis/Stiffness in Nondiabetic Heart Failure: A Multimodality Study.

JACC Cardiovasc Imaging 2021 02 29;14(2):393-407. Epub 2020 Oct 29.

Department of Cardiology, Mount Sinai School of Medicine, New York, New York, USA. Electronic address:

Objectives: The purpose of this study was to investigate the effect of empagliflozin on diastolic function in a nondiabetic heart failure with reduced ejection fraction (HFrEF) scenario and on the pathways causing diastolic dysfunction.

Background: This group demonstrated that empagliflozin ameliorates adverse cardiac remodeling, enhances myocardial energetics, and improves left ventricular systolic function in a nondiabetic porcine model of HF. Whether empagliflozin also improves diastolic function remains unknown. Read More

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February 2021

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells.

Int J Mol Sci 2020 Oct 21;21(20). Epub 2020 Oct 21.

Division of Cardiology, Istituto Nazionale Tumori- IRCCS- Fondazione G. Pascale, 80131 Napoli, Italy.

Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. Read More

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October 2020

Long-term effects of empagliflozin on excitation-contraction-coupling in human induced pluripotent stem cell cardiomyocytes.

J Mol Med (Berl) 2020 12 9;98(12):1689-1700. Epub 2020 Oct 9.

Department of Internal Medicine II, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.

The SGLT2 inhibitor empagliflozin improved cardiovascular outcomes in patients with diabetes. As the cardiac mechanisms remain elusive, we investigated the long-term effects (up to 2 months) of empagliflozin on excitation-contraction (EC)-coupling in human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CM) in a blinded manner. IPSC from 3 donors, differentiated into pure iPSC-CM (4 differentiations), were treated with a clinically relevant concentration of empagliflozin (0. Read More

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December 2020

Empagliflozin inhibits Na /H exchanger activity in human atrial cardiomyocytes.

ESC Heart Fail 2020 Sep 18. Epub 2020 Sep 18.

Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.

Aims: Recent clinical trials have proven gliflozins to be cardioprotective in diabetic and non-diabetic patients. However, the underlying mechanisms are incompletely understood. A potential inhibition of cardiac Na /H exchanger 1 (NHE1) has been suggested in animal models. Read More

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September 2020

Effects of Secretome from Fat Tissues on Ion Currents of Cardiomyocyte Modulated by Sodium-Glucose Transporter 2 Inhibitor.

Molecules 2020 Aug 8;25(16). Epub 2020 Aug 8.

Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.

Sodium-glucose transporter 2 (SGLT2) inhibitors were shown to decrease mortality from cardiovascular diseases in the EMPA-REG trial. However, the effects of empagliflozin (EMPA) for cardiac arrhythmia are not yet clarified. A total of 20 C57BL/6J mice were divided into four groups: (1) The control group were fed standard chow, (2) the metabolic syndrome (MS) group were fed a high-fat diet, (3) the empagliflozin (EMPA) group were fed a high-fat diet and empagliflozin 10 mg/kg daily, and (4) the glibenclamide (GLI) group were fed a high-fat diet and glibenclamide 0. Read More

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Tackling myocardial oxidative stress with empagliflozin: are we big enough to fight heart failure with preserved ejection fraction?

Cardiovasc Res 2021 01;117(2):343-345

Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, Schlieren, CH-8952, Switzerland.

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January 2021

Empagliflozin protects heart from inflammation and energy depletion via AMPK activation.

Pharmacol Res 2020 08 17;158:104870. Epub 2020 May 17.

Division of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address:

Aims: Sodium-glucose co-transporter 2 (SGLT2) were originally developed as kidney-targeting anti-diabetic drugs. However, due to their beneficial cardiac off-target effects (as SGLT2 is not expressed in the heart), these antagonists currently receive intense clinical interest in the context of heart failure (HF) in patients with or without diabetes mellitus (DM). Since the mechanisms by which these beneficial effects are mediated are still unclear yet, inflammation that is present in DM and HF has been proposed as a potential pharmacological intervention strategy. Read More

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Empagliflozin prevents doxorubicin-induced myocardial dysfunction.

Cardiovasc Diabetol 2020 05 15;19(1):66. Epub 2020 May 15.

Division of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.

Background: Empagliflozin showed efficacy in controlling glycaemia, leading to reductions in HbA1c levels, weight loss and blood pressure, compared to standard treatment. Moreover, the EMPA-REG OUTCOME trial demonstrated a 14% reduction of major adverse cardiovascular events (MACE), a 38% reduction in cardiovascular (CV) death and a 35% reduction in the hospitalization rate for heart failure (HF). These beneficial effect on HF were apparently independent from glucose control. Read More

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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 01;117(2):495-507

Department of Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany.

Aims: Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated the mechanisms of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF).

Methods And Results: The acute mechanisms of empagliflozin were investigated in human myocardium from patients with HFpEF and murine ZDF obese rats, which were treated in vivo. Read More

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January 2021

It's Not All About the Cardiomyocyte: Fibroblasts, Empagliflozin, and Cardiac Remodelling.

Can J Cardiol 2020 04 19;36(4):464-466. Epub 2019 Oct 19.

Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada. Electronic address:

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Empagliflozin attenuates ischemia and reperfusion injury through LKB1/AMPK signaling pathway.

Mol Cell Endocrinol 2020 02 21;501:110642. Epub 2019 Nov 21.

Department of Physiology and Biophysics, University of Mississippi Medical Center, 39216, Jackson, MS, USA; Department of Surgery, Morsani College of Medicine, University of South Florida, 33612, Tampa, FL, USA. Electronic address:

The beneficial effects of empagliflozin (EMPA) on cardiac functions during ischemia and reperfusion were characterized. The contractile functions of isolated cardiomyocytes from adult C57BL/6J mice were determined with IonOptix SoftEdgeMyoCam system. The mitochondrial superoxide production was measured by MitoSOX fluorescent probe. Read More

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February 2020

Empagliflozin Attenuates Myocardial Sodium and Calcium Dysregulation and Reverses Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats.

Int J Mol Sci 2019 Apr 4;20(7). Epub 2019 Apr 4.

Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.

Diabetes mellitus (DM) has significant effects on cardiac calcium (Ca) and sodium (Na⁺) regulation. Clinical studies have shown that empagliflozin (Jardiance™) has cardiovascular benefits, however the mechanisms have not been fully elucidated. This study aimed to investigate whether empagliflozin modulates cardiac electrical activity as well as Ca/Na⁺ homeostasis in DM cardiomyopathy. Read More

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SGLT2 inhibitors and cardioprotection: a matter of debate and multiple hypotheses.

Postgrad Med 2019 Mar;131(2):82-88

b Department of Internal Medicine, School of Medicine , University of Ioannina , Ioannina , Greece.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. Two trials have shown significant reductions of cardiovascular (CV) events with empagliflozin and canagliflozin, which could not be attributed solely to their antidiabetic effects. The aim of the review is the critical presentation of suggested mechanisms/hypotheses for the SGLT2 inhibitors' cardioprotection. Read More

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Delayed ischaemic contracture onset by empagliflozin associates with NHE1 inhibition and is dependent on insulin in isolated mouse hearts.

Cardiovasc Res 2019 Aug;115(10):1533-1545

Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam Infection & Immunity, Meibergdreef 9, AZ Amsterdam, The Netherlands.

Aims: Sodium glucose cotransporter 2 (SGLT2) inhibitors have sodium-hydrogen exchanger (NHE) inhibition properties in isolated cardiomyocytes, but it is unknown whether these properties extend to the intact heart during ischaemia-reperfusion (IR) conditions. NHE inhibitors as Cariporide delay time to onset of contracture (TOC) during ischaemia and reduce IR injury. We hypothesized that, in the ex vivo heart, Empagliflozin (Empa) mimics Cariporide during IR by delaying TOC and reducing IR injury. Read More

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Direct Cardiac Actions of Sodium Glucose Cotransporter 2 Inhibitors Target Pathogenic Mechanisms Underlying Heart Failure in Diabetic Patients.

Front Physiol 2018 21;9:1575. Epub 2018 Nov 21.

Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, Netherlands.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) are the first antidiabetic compounds that effectively reduce heart failure hospitalization and cardiovascular death in type 2 diabetics. Being explicitly designed to inhibit SGLT2 in the kidney, SGLT2i have lately been investigated for their off-target cardiac actions. Here, we review the direct effects of SGLT2i Empagliflozin (Empa), Dapagliflozin (Dapa), and Canagliflozin (Cana) on various cardiac cell types and cardiac function, and how these may contribute to the cardiovascular benefits observed in large clinical trials. Read More

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November 2018

Empagliflozin directly improves diastolic function in human heart failure.

Eur J Heart Fail 2018 12 17;20(12):1690-1700. Epub 2018 Oct 17.

Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.

Aims: Empagliflozin, a clinically used oral antidiabetic drug that inhibits the sodium-dependent glucose co-transporter 2, has recently been evaluated for its cardiovascular safety. Surprisingly, empagliflozin reduced mortality and hospitalization for heart failure (HF) compared to placebo. However, the underlying mechanisms remain unclear. Read More

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December 2018

Single dose of empagliflozin increases in vivo cardiac energy status in diabetic db/db mice.

Cardiovasc Res 2018 12;114(14):1843-1844

Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, Eindhoven, The Netherlands.

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December 2018