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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.

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Abbreviations

EBM:

endothelial basal medium

EGM:

endothelial growth medium

eNOS:

endothelial NO synthase

HUVEC:

human umbilical vein endothelial cells

MLCK:

myosin light chain kinase

MLCP:

myosin light chain phosphatase

MYPT1:

myosin phosphatase target subunit 1

RLC:

myosin regulatory light chain

ROCK:

RhoA-associated protein kinase

ROS:

reactive oxygen species

TER:

transendothelial electric resistance

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Acknowledgments

The work was supported by the Russian Science Foundation (project no. 19-15-00361; studies of HUVEC viability and long-term ECIS experiments) and Russian Foundation for Basic Research (project no. 20-015-00565; other experiments).

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Authors and Affiliations

  1. Institute of Experimental Cardiology, Chazov National Medical Research Center for Cardiology, 121552, Moscow, Russia

    Asker Y. Khapchaev, Olga A. Antonova, Olga A. Kazakova, Mikhail V. Samsonov, Alexander V. Vorotnikov & Vladimir P. Shirinsky

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  1. Asker Y. Khapchaev
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  2. Olga A. Antonova
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  3. Olga A. Kazakova
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  4. Mikhail V. Samsonov
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Contributions

K.A.Y., V.A.V., and S.V.P. developed the study concept and methodology; K.A.Y., A.O.A., S.M.V., K.O.A., and V.A.V. performed the experiments; K.A.Y. and V.A.V. curated the data; K.A.Y. and V.A.V. wrote the manuscript; K.A.Y., V.A.V., and S.V.P. supervised the study; K.A.Y. and S.V.P. acquired the funding.

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Correspondence to Asker Y. Khapchaev.

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The authors declare no conflict of interest. This article does not contain description of studies with the involvement of humans or animal subjects performed by any of the authors.

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Khapchaev, A.Y., Antonova, O.A., Kazakova, O.A. et al. Long-Term Experimental Hyperglycemia Does Not Impair Macrovascular Endothelial Barrier Integrity and Function in vitro. Biochemistry Moscow 88, 1126–1138 (2023). https://doi.org/10.1134/S0006297923080072

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