ArticleBasic research in cardiology2024
Empagliflozin prevents heart failure through inhibition of the NHE1-NO pathway, independent of SGLT2.
Article in Basic research in cardiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Effects of Dapagliflozin Combined with Sacubitril/Valsartan on Cardiac Electrophysiology and Quantitative Myocardial Motion Parameters in Patients with Atrial Fibrillation and Heart Failure with Preserved Ejection Fraction.Cardiovascular drugs and therapy · 2026Article
- SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.Molecular biomedicine · 2026Review
- Protective Effect of the NHE1 Inhibitor Buthutin A on Oxidative Stress-Induced Apoptosis in HUVECs.ACS omega · 2026Article
- Empagliflozin restores cardiac function in obese-diabetic HFpEF mice but further alters gene expression.Basic research in cardiology · 2026Article
- SGLT2 inhibition improves sarcomere contractile dysfunction in human models of dilated cardiomyopathy.Journal of translational medicine · 2026Article
- Emerging Role of Sodium-Glucose Cotransporter-2 Inhibitors in Aortic Stenosis.JACC. Basic to translational science · 2026Review
- Sodium-glucose cotransporter 2 inhibitors in breast cancer patients on endocrine therapy: a targeted strategy to mitigate long-term cardiometabolic risk.Journal of translational medicine · 2026Review
- Organ-Specific Efficacy of Postischemic Empagliflozin in Acute Stroke and Myocardial Infarction Using Preclinical Models.Journal of the American Heart Association · 2026Article
- Empagliflozin improves metabolism and prevents myocardial and coronary dysfunction in streptozotocin-diabetic and non-diabetic rats subjected to ischemia/reperfusion.Basic research in cardiology · 2026Article
- Review
- Empagliflozin Alleviates Osteoarthritis Progression by Attenuating Inflammation, Restoring Impaired Autophagy, and Ameliorating Chondrocyte Senescence.Biomedicines · 2026Article
- Mechanisms and Therapeutic Potential of Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure.Reviews in cardiovascular medicine · 2026Review
- Mitochondrial Homeostasis in Diabetic Cardiomyopathy: From Dysfunction to Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- The SGLT2 Inhibitor Canagliflozin Promotes β-Cell Regeneration and Restores and Stabilises β-Cell Identity in a Polygenic Model of Severe Early-Onset Type 2 Diabetes.Journal of cellular and molecular medicine · 2026Article
- Use of SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitors in Pulmonary Hypertension.Circulation. Heart failure · 2026Review
- Empagliflozin-pirfenidone dual therapy improves cardiac function and structure in a preclinical two-hit HFpEF model.Frontiers in pharmacology · 2026Article
- Chronic cardiorenal syndrome: cardio-renal protective effect of SGLT2i.Renal failure · 2025Review
- SGLT2 Inhibitors Confer Cardiovascular Protection via the Gut-Kidney-Heart Axis: Mechanisms and Translational Perspectives.Journal of cardiovascular development and disease · 2025Review
- Investigating the Role of Empagliflozin in the Pathological Progress of Ischemia-Reperfusion Injury in Rat Kidneys: The Involvement of Nitric Oxide.Advanced pharmaceutical bulletin · 2025Article
- Mechano-energetic uncoupling in heart failure.Nature reviews. Cardiology · 2025Review
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22 authors.
Funding
Abstract
Sodium glucose cotransporter 2 inhibitors (SGLT2i) constitute the only medication class that consistently prevents or attenuates human heart failure (HF) independent of ejection fraction. We have suggested earlier that the protective mechanisms of the SGLT2i Empagliflozin (EMPA) are mediated through reductions in the sodium hydrogen exchanger 1 (NHE1)-nitric oxide (NO) pathway, independent of SGLT2. Here, we examined the role of SGLT2, NHE1 and NO in a murine TAC/DOCA model of HF. SGLT2 knockout mice only showed attenuated systolic dysfunction without having an effect on other signs of HF. EMPA protected against systolic and diastolic dysfunction, hypertrophy, fibrosis, increased Nppa/Nppb mRNA expression and lung/liver edema. In addition, EMPA prevented increases in oxidative stress, sodium calcium exchanger expression and calcium/calmodulin-dependent protein kinase II activation to an equal degree in WT and SGLT2 KO animals. In particular, while NHE1 activity was increased in isolated cardiomyocytes from untreated HF, EMPA treatment prevented this. Since SGLT2 is not required for the protective effects of EMPA, the pathway between NHE1 and NO was further explored in SGLT2 KO animals. In vivo treatment with the specific NHE1-inhibitor Cariporide mimicked the protection by EMPA, without additional protection by EMPA. On the other hand, in vivo inhibition of NOS with L-NAME deteriorated HF and prevented protection by EMPA. In conclusion, the data support that the beneficial effects of EMPA are mediated through the NHE1-NO pathway in TAC/DOCA-induced heart failure and not through SGLT2 inhibition.
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