Trum, Maximilian and Riechel, Johannes and Wagner, Stefan (2021) Cardioprotection by SGLT2 Inhibitors-Does It All Come Down to Na+? INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (15): 7976. ISSN 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are emerging as a new treatment strategy for heart failure with reduced ejection fraction (HFrEF) and-depending on the wistfully awaited results of two clinical trials (DELIVER and EMPEROR-Preserved)-may be the first drug class to improve cardiovascular outcomes in patients suffering from heart failure with preserved ejection fraction (HFpEF). Proposed mechanisms of action of this class of drugs are diverse and include metabolic and hemodynamic effects as well as effects on inflammation, neurohumoral activation, and intracellular ion homeostasis. In this review we focus on the growing body of evidence for SGLT2i-mediated effects on cardiac intracellular Na+ as an upstream mechanism. Therefore, we will first give a short overview of physiological cardiomyocyte Na+ handling and its deterioration in heart failure. On this basis we discuss the salutary effects of SGLT2i on Na+ homeostasis by influencing NHE1 activity, late I-Na as well as CaMKII activity. Finally, we highlight the potential relevance of these effects for systolic and diastolic dysfunction as well as arrhythmogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LATE SODIUM CURRENT; CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE; HEART-FAILURE; INTRACELLULAR NA+; CARDIAC-HYPERTROPHY; NA+-CA2+ EXCHANGER; CYTOSOLIC NA+; CARDIOVASCULAR OUTCOMES; SARCOPLASMIC-RETICULUM; MOUSE CARDIOMYOCYTES; SGLT2 inhibitor; heart failure; HFrEF; HFpEF; arrhythmia; Na+; NHE1; late I-Na; CaMKII |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Petra Gürster |
| Date Deposited: | 16 Dec 2022 11:55 |
| Last Modified: | 16 Dec 2022 11:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46004 |
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