Mechanosensitive molecular interactions in atherogenic regions of the arteries: development of atherosclerosis.

E L Mishchenko,V A Ivanisenko,A M Mishchenko

doi:10.18699/vj21.062

Abstract

A terrible disease of the cardiovascular system, atherosclerosis, develops in the areas of bends and branches of arteries, where the direction and modulus of the blood flow velocity vector change, and consequently so does the mechanical effect on endothelial cells in contact with the blood flow. The review focuses on topical research studies on the development of atherosclerosis – mechanobiochemical events that transform the proatherogenic mechanical stimulus of blood flow – low and low/oscillatory arterial wall shear stress in the chains of biochemical reactions in endothelial cells, leading to the expression of specific proteins that cause the progression of the pathological process. The stages of atherogenesis, systemic risk factors for atherogenesis and its important hemodynamic factor, low and low/oscillatory wall shear stress exerted by blood flow on the endothelial cells lining the arterial walls, have been described. The interactions of cell adhesion molecules responsible for the development of atherosclerosis under low and low/oscillating shear stress conditions have been demonstrated. The activation of the regulator of the expression of cell adhesion molecules, the transcription factor NF-κB, and the factors regulating its activation under these conditions have been described. Mechanosensitive signaling pathways leading to the expression of NF-κB in endothelial cells have been described. Studies of the mechanobiochemical signaling pathways and interactions involved in the progression of atherosclerosis provide valuable information for the development of approaches that delay or block the development of this disease. Key words: atherogenesis; shear stress; transcription factor NF-κB; RelA expression; mechanosensitive receptors; cell adhesion molecules; signaling pathways; mechanotransduction.

Highlights

For citation: Mishchenko E.L., Mishchenko A.M., Ivanisenko V.A
The lateral displacement of vascular endothelial (VE)-cadherin in the membrane most likely occurs due to the destabilisation of the VE-cadherin bond with the actin cytoskeleton by the following mechanism: the ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) clusters in the sites of intercellular adhesion of the leukocytes to the endo thelial cells (ECs) induce the intracellular activation of the Src and Pyk2 tyrosine kinases and the phosphorylation of Tyr658 and Tyr731 of the cytoplasmic domain of VE-cadherin, which are involved in the low-affinity binding of VE-cadherin to p120- and β-catenin, respectively
The transcription factor NF-κB and the cell adhesion molecules ICAM-1, VCAM-1 and E-selectin are the earliest markers of atherogenesis

Summary

Introduction

For citation: Mishchenko E.L., Mishchenko A.M., Ivanisenko V.A. Mechanosensitive molecular interactions in athero genic regions of the arteries: development of atherosclerosis. The molecules of cell adhesion and their interactions in the early stage of atherogenesis OxLDLs in the subendothelial space as well as low and low/ oscillatory WSS cause pro-inflammatory activation of endo thelial cells (ECs), which leads to the rolling of leukocytes in the circulating blood flow to the endothelium, their adhesion

Results

Conclusion