Department of Anesthesiology - Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Cardiovascular Science, Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands.
Br J Pharmacol. 2022 Aug;179(16):4047-4062. doi: 10.1111/bph.15850. Epub 2022 Apr 22.
Sodium glucose co-transporter 2 inhibitors (SGLT-2is) improve cardiovascular outcomes in both diabetic and non-diabetic patients. Preclinical studies suggest that SGLT-2is directly affect endothelial function in a glucose-independent manner. The effects of SGLT-2is include decreased oxidative stress and inflammatory reactions in endothelial cells. Furthermore, SGLT2is restore endothelium-related vasodilation and regulate angiogenesis. The favourable cardiovascular effects of SGLT-2is could be mediated via a number of pathways: (1) inhibition of the overactive sodium-hydrogen exchanger; (2) decreased expression of nicotinamide adenine dinucleotide phosphate oxidases; (3) alleviation of mitochondrial injury; (4) suppression of inflammation-related signalling pathways (e.g., by affecting NF-κB); (5) modulation of glycolysis; and (6) recovery of impaired NO bioavailability. This review focuses on the most recent progress and existing gaps in preclinical investigations concerning the direct effects of SGLT-2is on endothelial dysfunction and the mechanisms underlying such effects.
钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT-2is）改善了糖尿病和非糖尿病患者的心血管结局。临床前研究表明，SGLT-2is 以葡萄糖非依赖性的方式直接影响内皮功能。SGLT-2is 的作用包括减少内皮细胞中的氧化应激和炎症反应。此外，SGLT2is 恢复与内皮相关的血管舒张并调节血管生成。SGLT-2is 的有利心血管作用可能通过多种途径介导：（1）抑制过度活跃的钠-氢交换器；（2）减少烟酰胺腺嘌呤二核苷酸磷酸氧化酶的表达；（3）缓解线粒体损伤；（4）抑制炎症相关信号通路（例如，通过影响 NF-κB）；（5）调节糖酵解；以及（6）恢复受损的一氧化氮生物利用度。本综述重点介绍了 SGLT-2is 对内皮功能障碍的直接作用以及这些作用的潜在机制的临床前研究的最新进展和现有差距。
