Khapchaev Asker Y, Antonova Olga A, Kazakova Olga A, Samsonov Mikhail V, Vorotnikov Alexander V, Shirinsky Vladimir P
Institute of Experimental Cardiology, Chazov National Medical Research Center for Cardiology, Moscow, 121552, Russia.
Biochemistry (Mosc). 2023 Aug;88(8):1126-1138. doi: 10.1134/S0006297923080072.
Hyperglycemia is a hallmark of type 2 diabetes implicated in vascular endothelial dysfunction and cardiovascular complications. Many in vitro studies identified endothelial apoptosis as an early outcome of experimentally modeled hyperglycemia emphasizing cell demise as a significant factor of vascular injury. However, endothelial apoptosis has not been observed in vivo until the late stages of type 2 diabetes. Here, we studied the long-term (up to 4 weeks) effects of high glucose (HG, 30 mM) on human umbilical vein endothelial cells (HUVEC) in vitro. HG did not alter HUVEC monolayer morphology, ROS levels, NO production, and exerted minor effects on the HUVEC apoptosis markers. The barrier responses to various clues were indistinguishable from those by cells cultured in physiological glucose (5 mM). Tackling the key regulators of cytoskeletal contractility and endothelial barrier revealed no differences in the histamine-induced intracellular Ca2+ responses, nor in phosphorylation of myosin regulatory light chain or myosin light chain phosphatase. Altogether, these findings suggest that vascular endothelial cells may well tolerate HG for relatively long exposures and warrant further studies to explore mechanisms involved in vascular damage in advanced type 2 diabetes.
高血糖是2型糖尿病的一个标志，与血管内皮功能障碍和心血管并发症有关。许多体外研究将内皮细胞凋亡确定为实验模拟高血糖的早期结果，强调细胞死亡是血管损伤的一个重要因素。然而，直到2型糖尿病晚期才在体内观察到内皮细胞凋亡。在此，我们在体外研究了高糖（HG，30 mM）对人脐静脉内皮细胞（HUVEC）的长期（长达4周）影响。高糖并未改变HUVEC单层形态、活性氧水平、一氧化氮生成，对HUVEC凋亡标志物的影响较小。对各种刺激的屏障反应与在生理葡萄糖（5 mM）中培养的细胞没有区别。研究细胞骨架收缩性和内皮屏障的关键调节因子发现，组胺诱导的细胞内Ca2+反应、肌球蛋白调节轻链或肌球蛋白轻链磷酸酶的磷酸化没有差异。总之，这些发现表明血管内皮细胞可能能够在相对长时间暴露于高糖环境下良好耐受，这值得进一步研究以探索晚期2型糖尿病血管损伤所涉及的机制。
