Cellular Senescence Affects Cardiac Regeneration and Repair in Ischemic Heart Disease.

Chi Yan,Weiqiang Huang,Zhimeng Xu

doi:10.14336/ad.2020.0811

Abstract

Ischemic heart disease (IHD) is defined as a syndrome of ischemic cardiomyopathy. Myogenesis and angiogenesis in the ischemic myocardium are important for cardiomyocyte (CM) survival, improving cardiac function and decreasing the progression of heart failure after IHD. Cellular senescence is a state of permanent irreversible cell cycle arrest caused by stress that results in a decline in cellular functions, such as proliferation, migration, homing, and differentiation. In addition, senescent cells produce the senescence-associated secretory phenotype (SASP), which affects the tissue microenvironment and surrounding cells by secreting proinflammatory cytokines, chemokines, growth factors, and extracellular matrix degradation proteins. The accumulation of cardiovascular-related senescent cells, including vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), CMs and progenitor cells, is an important risk factor of cardiovascular diseases, such as vascular aging, atherosclerotic plaque formation, myocardial infarction (MI) and ventricular remodeling. This review summarizes the processes of angiogenesis, myogenesis and cellular senescence after IHD. In addition, this review focuses on the relationship between cellular senescence and cardiovascular disease and the mechanism of cellular senescence. Finally, we discuss a potential therapeutic strategy for MI targeting senescent cells.

Highlights

Cardiovascular disease is the leading cause of death among noncommunicable diseases, and ischemic heart disease (IHD) is the number one cause of cardiovascular disease-related death[1]
Senescence in CMs, vascular cells and stem/progenitor cells entails a decreased replicative capacity and cellular dysfunction, which contribute to cardiovascular aging and impairment of the reparative and regenerative potential [20, 21].This review summarizes the mechanisms of cellular senescence and the senescence-associated secretory phenotype (SASP) and the effects of cellular senescence on the process of IHD to illuminate potential therapies targeting senescent cells
Since senescent cells are potentially involved in cardiac vascular disease processes, avoiding the risk factors that induce cellular senescence, eliminating senescent cells and attenuating the SASP have emerged as attractive therapeutic strategies (Table 2)

Summary

Introduction

Cardiovascular disease is the leading cause of death among noncommunicable diseases, and ischemic heart disease (IHD) is the number one cause of cardiovascular disease-related death[1]. The transcription factor (TF) STAT plays a major role in regulating the expression of genes related to cell cycle progression, differentiation, proliferation and apoptosis [79]. The level of NAD+ in ECs decreases, resulting in a decrease in SIRT1 activity and a decrease in the ability of endothelial cells to survive oxidative stress and respond to growth factor signals [89].

Results

Conclusion