期刊
JACC-BASIC TO TRANSLATIONAL SCIENCE
卷 4, 期 5, 页码 575-591出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2019.04.003
关键词
contraction and relaxation; endothelial cell-derived nitric oxide; empagliflozin; heart failure; oxidative stress
资金
- CVON-RECONNECT from the Netherlands CardioVascular Research Initiative
- Dutch Heart Foundation
- Dutch Federation of University Medical Centers
- Netherlands Organization for Health Research and Development
- Royal Netherlands Academy of Science
The positive findings of the EMPA-REG OUTCOME trial (Randomized, Placebo-Controlled Cardiovascular Outcome Trial of Empagliflozin) on heart failure (HF) outcome in patients with type 2 diabetes mellitus suggest a direct effect of empagliflozin on the heart. These patients frequently have HF with preserved ejection fraction (HFpEF), in which a metabolic risk-related pro-inflammatory state induces cardiac microvascular endothelial cell (CMEC) dysfunction with subsequent cardiomyocyte (CM) contractility impairment. This study showed that CMECs confer a direct positive effect on contraction and relaxation of CMs, an effect that requires nitric oxide, is diminished after CMEC stimulation with tumor necrosis factor-alpha, and is restored by empagliflozin. Our findings on the effect of empagliflozin on CMEC-mediated preservation of CM function suggests that empagliflozin can be used to treat the cardiac mechanical implications of microvascular dysfunction in HFpEF. (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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