Trum, Maximilian and Riechel, Johannes and Lebek, Simon and Pabel, Steffen and Sossalla, Samuel T. and Hirt, Stephan and Arzt, Michael and Maier, Lars S. and Wagner, Stefan (2020) Empagliflozin inhibits Na+/H(+)exchanger activity in human atrial cardiomyocytes. ESC HEART FAILURE, 7 (6). pp. 4429-4437. ISSN 2055-5822,
Full text not available from this repository. (Request a copy)Abstract
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. We investigated the effect of empagliflozin on NHE1 activity in human atrial cardiomyocytes. Methods and results Expression of NHE1 was assessed in human atrial and ventricular tissue via western blotting. NHE activity was measured as the maximal slope of pH recovery after NH(4)(+)pulse in isolated carboxy-seminaphtarhodafluor 1 (SNARF1)-acetoxymethylester-loaded murine ventricular and human atrial cardiomyocytes. NHE1 is abundantly expressed in human atrial and ventricular tissue. Interestingly, compared with patients without heart failure (HF), atrial NHE1 expression was significantly increased in patients with HF with preserved ejection fraction and atrial fibrillation. The largest increase in atrial and ventricular NHE1 expression, however, was observed in patients with end-stage HF undergoing heart transplantation. Importantly, acute exposure to empagliflozin (1 mu mol/L, 10 min) significantly inhibited NHE activity to a similar extent in human atrial myocytes and mouse ventricular myocytes. This inhibition was also achieved by incubation with the well-described selective NHE inhibitor cariporide (10 mu mol/L, 10 min). Conclusions This is the first study systematically analysing NHE1 expression in human atrial and ventricular myocardium of HF patients. We show that empagliflozin inhibits NHE in human cardiomyocytes. The extent of NHE inhibition was comparable with cariporide and may potentially contribute to the improved outcome of patients in clinical trials.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NA+/H+-EXCHANGER; HEART-FAILURE; CARDIAC-HYPERTROPHY; CA2+; SGLT2 inhibitor; Empagliflozin; Na+/H(+)exchanger 1; Heart failure |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2021 11:32 |
| Last Modified: | 11 Mar 2021 11:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43778 |
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