ENDOTHELIAL DYSFUNCTION IN TYPE 2 DIABETES. Review

Abstract

Relevance. The problem of systematization and refinement of modern concepts of the pathogenesis of endothelial dysfunction (EDF) and its role in the development of microvascular complications of type 2 diabetes mellitus (T2DM) is relevant due to the lack of pathogenetic treatment nowadays, which would include endothelial dysfunction. Objective: to conduct an analytical review of the results of scientific research on the mechanisms of EDF in T2DM, with the aim of proposing an integrated modern concept of the pathogenesis of EDF. Materials and methods. Review of scientific publications in the international electronic scientific databases of PubMed, Embase and Scopus for keywords for the entire available period (1982-2019). Results. The article provides modern data on the modern concept of the pathogenesis of EDF and its role in the development of microvascular complications in T2DM. The pathogenesis of EDF in type 2 diabetes mellitus is based on the following key mechanisms: impaired synthesis of the endothelial fraction of nitric oxide (NO) due to inhibition of the activity of endothelial NO synthase (eNOS); decreased bioavailability of NO because of oxidative stress; activation of the formation of Endothelin-1 (ET1) and expression of endothelin receptors with a predominance of vasoconstriction; inflammation, which is supported by the synthesis of pro-inflammatory cytokines and causes the expression of inducible NO synthase (iNOS), which stimulates the synthesis of a significant amount of NO, which enters into free radical reactions with the formation of cytotoxic products. Conclusions. The pathogenesis of endothelial dysfunction is impaired nitric oxide synthesis. Endothelial dysfunction, as an integral mechanism, underlies in the core mechanisms the development of vascular complications in type 2 diabetes.

Keywords

• diabetes mellitus 2 type, endothelim, endothelium disfunction, micro- and macrovascular complications