New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death

Author:

Bu Lan-Lan1,Yuan Huan-Huan2,Xie Ling-Li23,Guo Min-Hua2,Liao Duan-Fang1,Zheng Xi-Long3ORCID

Affiliation:

1. School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China

2. College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China

3. Departments of Biochemistry and Molecular Biology and Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada

Abstract

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

Funder

Canadian Institutes of Health Research

Natural Sciences and Engineering Research Council of Canada

Key Discipline of Basic Medicine, Hunan University of Chinese Medicine

Science and Technology Innovation Program of Hunan Province

Key Laboratory of Vascular Biology and Translational Medicine, Hunan University of Chinese Medicine

Basic Research Center of Integrated Chinese and Western Medicine for Prevention and Treatment of Vascular Diseases, Medical School, Hunan University of Chinese Medicine

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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