PDF(Pubmed)
Abstract：
Endothelial dysfunction often precedes the development of cardiovascular diseases, including heart failure. The cardioprotective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) could be explained by their favorable impact on the endothelium. In this review, we summarize the current knowledge on the direct in vitro effects of SGLT2is on endothelial cells, as well as the systematic observations in preclinical models. Four putative mechanisms are explored: oxidative stress, nitric oxide (NO)-mediated pathways, inflammation, and endothelial cell survival and proliferation. Both in vitro and in vivo studies suggest that SGLT2is share a class effect on attenuating reactive oxygen species (ROS) and on enhancing the NO bioavailability by increasing endothelial nitric oxide synthase activity and by reducing NO scavenging by ROS. Moreover, SGLT2is significantly suppress inflammation by preventing endothelial expression of adhesion receptors and pro-inflammatory chemokines in vivo, indicating another class effect for endothelial protection. However, in vitro studies have not consistently shown regulation of adhesion molecule expression by SGLT2is. While SGLT2is improve endothelial cell survival under cell death-inducing stimuli, their impact on angiogenesis remains uncertain. Further experimental studies are required to accurately determine the interplay among these mechanisms in various cardiovascular complications, including heart failure and acute myocardial infarction.
摘要：
内皮功能障碍往往先于心血管疾病的发展，包括心力衰竭.钠-葡萄糖协同转运蛋白2抑制剂（SGLT2is）的心脏保护益处可以通过它们对内皮的有利影响来解释。在这次审查中,我们总结了SGLT2is对内皮细胞的直接体外作用的现有知识，以及临床前模型中的系统观察。探索了四种推定机制：氧化应激，一氧化氮（NO）介导的途径，炎症,和内皮细胞的存活和增殖。体外和体内研究均表明，SGLT2通过增加内皮型一氧化氮合酶活性和减少ROS清除NO，对减弱活性氧（ROS）和增强NO生物利用度具有一类作用。此外，SGLT2通过在体内阻止粘附受体和促炎趋化因子的内皮表达来显著抑制炎症,表明内皮保护的另一类效应。然而,体外研究没有一致地显示SGLT2is对粘附分子表达的调节。虽然SGLT2在诱导细胞死亡的刺激下改善内皮细胞的存活，它们对血管生成的影响仍不确定。需要进一步的实验研究来准确确定这些机制在各种心血管并发症中的相互作用。包括心力衰竭和急性心肌梗死。
