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Review
. 2023 Oct 13;24(20):15160.
doi: 10.3390/ijms242015160.

New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death

Lan-Lan Bu  1 , Huan-Huan Yuan  2 , Ling-Li Xie  2   3 , Min-Hua Guo  2 , Duan-Fang Liao  1 , Xi-Long Zheng  3
Affiliations
Review

New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death

Lan-Lan Bu et al. Int J Mol Sci. .

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.

Keywords: atherosclerosis; endothelial cell; endothelial cell death; endothelial cell senescence.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Oxidative stress and EC senescence. Green pointed arrows indicate stimulation; red blunted arrows indicate inhibition.
Figure 2
Figure 2
Inflammation and EC senescence. Green pointed arrows indicate stimulation; red blunted arrows indicate inhibition.
Figure 3
Figure 3
Genomic instability and EC senescence. Green pointed arrows indicate stimulation; red blunted arrows indicate inhibition.
Figure 4
Figure 4
Metabolite-sensing longevity pathways and EC senescence. Green pointed arrows indicate stimulation; red blunted arrows indicate inhibition.
Figure 5
Figure 5
Activated RAS and EC senescence. Green pointed arrows indicate stimulation; red blunted arrows indicate inhibition.
Figure 6
Figure 6
Uric acid and EC senescence. Green pointed arrows indicate stimulation; red blunted arrows indicate inhibition.
Figure 7
Figure 7
Polyploidization and EC senescence. Green pointed arrows indicate stimulation; red blunted arrows indicate inhibition.
Figure 8
Figure 8
Timeline of cell death research.
Figure 9
Figure 9
EC death in atherosclerosis. Green pointed arrows indicate stimulation; red blunted arrows indicate inhibition.
See this image and copyright information in PMC

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