Cardiac Microvascular Endothelial Enhancement of Cardiomyocyte Function Is Impaired by Inflammation and Restored by Empagliflozin
Cardiac Microvascular Endothelial Enhancement of Cardiomyocyte Function Is Impaired by Inflammation and Restored by Empagliflozin
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DOI：
10.1016/j.jacbts.2019.04.003
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发表时间：
2019-09-01
影响因子：
9.7
通讯作者：
van Hinsbergh, Victor W. M.
中科院分区：
文献类型：
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作者：
Juni, Rio P.;Kuster, Diederik W. D.;van Hinsbergh, Victor W. M.
EMPA-REG结果试验(Emagliflzin的随机、安慰剂控制的心血管结果试验)对2型糖尿病患者的心力衰竭(HF)结果的阳性结果表明，Emagliflzin对心脏有直接作用。这些患者经常患有射血分数(HFpEF)保留的心衰，在这种情况下，代谢风险相关的促炎状态会导致心脏微血管内皮细胞(CMEC)功能障碍，随后心肌细胞(CM)收缩功能受损。本研究表明，CMECs对CMS的收缩和松弛有直接的正向作用，这种作用需要一氧化氮，在肿瘤坏死因子-α刺激CMEC后，这种作用被减弱，并被依帕格列酮恢复。我们的研究结果表明，埃帕利福秦对CMEC介导的心肌功能保护的影响表明，埃帕利福秦可用于治疗HFpEF中微血管功能障碍所致的心脏力学损害。(C)2019年提交人。由爱思唯尔公司代表美国心脏病学会基金会出版。
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.