Endothelial Shear Stress and Atherosclerosis: From Mechanisms to Therapeutics

42 Pages Posted: 1 Dec 2021

See all articles by Lei He

Lei He

The Chinese University of Hong Kong

Cheng-Lin Zhang

Shenzhen University

Qinghua Chen

The Chinese University of Hong Kong (CUHK) - School of Biomedical Sciences

Li Wang

City University of Hong Kong (CityU) - Department of Biomedical Sciences

Yu Huang

City University of Hong Kong (CityU) - Department of Biomedical Sciences

Abstract

Atherosclerotic vascular disease and its complications are among the top causes of mortality worldwide. In the vascular lumen, atherosclerotic plaques are not randomly distributed. Instead, they are preferentially localized at the curvature and bifurcations along the arterial tree, where shear stress is lower or disturbed. Numerous studies demonstrate that endothelial cell phenotypic change (e.g., inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, endothelial-mesenchymal transition, and endothelial barrier disruption) in duced by oscillatory shear force plays fundamental roles in the initiation and progression of atherosclerosis. Mechano-sensors, adaptor proteins, kinases, and transcriptional factors work closely at different layers to transduce the shear stress force from the plasma membrane to the nucleus in endothelial cells, thereby controlling the expression of genes that determine cell fate and phenotype. An in-depth understanding of these mechano-sensitive signaling cascades shall provide new translational strategies for therapeutic intervention of atherosclerotic vascular disease. This review updates the recent advances of endothelial mechano-transduction and its role in the pathogenesis of atherosclerosis, and highlights the perpective of new anti-atherosclerosis therapies through targeting these mechano-regulated signaling molecules.

Note:
Funding: This work was supported by grants from Hong Kong RGC-Collaborative Research Fund (C4024-16W), Hong Kong RGC-Senior Research Fellow Scheme (SRFS2021-4S04), RGC-General Research Fund (14109720, 14109618, 14164817), National Natural Science Foundation of China (91939302, 82000056), and a startup fund from City University of Hong Kong

Declaration of Interests: None

Keywords: Atherosclerosis, Mechano-transduction, Shear stress, Endothelial cells, inflammation, oxidative stress, Therapies

Suggested Citation

He, Lei and Zhang, Cheng-Lin and Chen, Qinghua and Wang, Li and Huang, Yu, Endothelial Shear Stress and Atherosclerosis: From Mechanisms to Therapeutics. Available at SSRN: https://ssrn.com/abstract=3975295 or http://dx.doi.org/10.2139/ssrn.3975295

Lei He

The Chinese University of Hong Kong ( email )

Cheng-Lin Zhang

Shenzhen University ( email )

3688 Nanhai Road, Nanshan District
Shenzhen, 518060
China

Qinghua Chen

The Chinese University of Hong Kong (CUHK) - School of Biomedical Sciences ( email )

China

Li Wang

City University of Hong Kong (CityU) - Department of Biomedical Sciences ( email )

Hong Kong
China

Yu Huang (Contact Author)

City University of Hong Kong (CityU) - Department of Biomedical Sciences ( email )

Hong Kong
China

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