Effects of shear stress on vascular endothelial functions in atherosclerosis and potential therapeutic approaches

Abstract

Different blood flow patterns in the arteries can alter the adaptive phenotype of vascular endothelial cells (ECs), thereby affecting the functions of ECs and are directly associated with the occurrence of lesions in the early stages of atherosclerosis (AS). Atherosclerotic plaques are commonly found at curved or bifurcated arteries, where the blood flow pattern is dominated by oscillating shear stress (OSS). OSS can induce ECs to transform into pro-inflammatory phenotypes, increase cellular inflammation, oxidative stress response, mitochondrial dysfunction, metabolic abnormalities and endothelial permeability, thereby promoting the progression of AS. On the other hand, the straight artery has a stable laminar shear stress (LSS), which promotes the transformation of ECs into an anti-inflammatory phenotype, improves endothelial cell function, thereby inhibits atherosclerotic progression. ECs have the ability to actively sense, integrate, and convert mechanical stimuli by shear stress into biochemical signals that further induces intracellular changes (such as the opening and closing of ion channels, activation and transcription of signaling pathways). Here we not only outline the relationship between functions of vascular ECs and different forms of fluid shear stress in AS, but also aim to provide new solutions for potential atherosclerotic therapies targeting intracellular mechanical transductions.

Keywords: Atherosclerosis; Endothelial cells; Mechanotransduction; Mitochondrial homeostasis; Shear stress; Therapies.