Long-term experimental hyperglycemia does not impair macrovascular endothelial barrier integrity and function in vitro

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Abstract

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.

About the authors

A. Y Khapchaev

Institute of Experimental Cardiology, E. I. Chazov National Medical Research Center for Cardiology

Email: AYKhapchaev@cardio.ru
121552 Moscow, Russia

O. A Antonova

Institute of Experimental Cardiology, E. I. Chazov National Medical Research Center for Cardiology

121552 Moscow, Russia

O. A Kazakova

Institute of Experimental Cardiology, E. I. Chazov National Medical Research Center for Cardiology

121552 Moscow, Russia

M. V Samsonov

Institute of Experimental Cardiology, E. I. Chazov National Medical Research Center for Cardiology

121552 Moscow, Russia

A. V Vorotnikov

Institute of Experimental Cardiology, E. I. Chazov National Medical Research Center for Cardiology

121552 Moscow, Russia

V. P Shirinsky

Institute of Experimental Cardiology, E. I. Chazov National Medical Research Center for Cardiology

121552 Moscow, Russia

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