Dimitriadis Kyriakos, Adamopoulou Eleni, Pyrpyris Nikolaos, Sakalidis Athanasios, Leontsinis Ioannis, Manta Eleni, Mantzouranis Emmanouil, Beneki Eirini, Soulaidopoulos Stergios, Konstantinidis Dimitrios, Fragkoulis Christos, Aggeli Konstantina, Tsioufis Konstantinos
First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece.
Eur Heart J Cardiovasc Pharmacother. 2023 Dec 14;9(8):741-757. doi: 10.1093/ehjcvp/pvad053.
The beneficial cardiovascular effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors irrespective of the presence of diabetes mellitus are nowadays well established and they already constitute a significant pillar for the management of heart failure, irrespective of the ejection fraction. The exact underlying mechanisms accountable for these effects, however, remain largely unknown. The direct effect on endothelial function and microcirculation is one of the most well studied. The broad range of studies presented in this review aims to link all available data from the bench to bedside and highlight the existing gaps as well as the future directions in the investigations concerning the effects of SGLT2 inhibitors on the endothelium and the microcirculation.
An extensive search has been conducted using the MEDLINE/PubMed database in order to identify the relevant studies. Preclinical data suggest that SGLT2 inhibitors directly affect endothelial function independently of glucose and specifically via several interplaying molecular pathways, resulting in improved vasodilation, increased NO production, enhanced mitochondrial homeostasis, endothelial cell viability, and angiogenesis as well as attenuation of oxidative stress and inflammation. Clinical data systematically confirm this beneficial effect on the endothelium, whereas the evidence concerning the effect on the microcirculation is conflicting.
Preclinical and clinical studies indicate that SGLT2 inhibitors attenuate endothelial and microvascular dysfunction via a combination of mechanisms, which play a role in their beneficial cardiovascular effect.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对心血管有益的作用，无论是否存在糖尿病，如今已得到充分证实，并且它们已经构成了心力衰竭管理的重要支柱，无论射血分数如何。然而，导致这些作用的确切潜在机制在很大程度上仍然未知。对内皮功能和微循环的直接影响是研究最为充分的方面之一。本综述中呈现的广泛研究旨在将从实验台到临床的所有可用数据联系起来，并突出关于SGLT2抑制剂对内皮和微循环影响的研究中存在的差距以及未来方向。
使用MEDLINE/PubMed数据库进行了广泛搜索以识别相关研究。临床前数据表明，SGLT2抑制剂独立于葡萄糖直接影响内皮功能，具体通过几种相互作用的分子途径，导致血管舒张改善、一氧化氮生成增加、线粒体稳态增强、内皮细胞活力和血管生成增加，以及氧化应激和炎症减轻。临床数据系统地证实了对内皮的这种有益作用，而关于对微循环影响的证据则相互矛盾。
临床前和临床研究表明，SGLT2抑制剂通过多种机制减轻内皮和微血管功能障碍，这些机制在其有益的心血管作用中发挥作用。
