Chapter 9 - Vascular diseases: atherosclerosis and atherosclerotic cardiovascular diseases

Abstract

Atherosclerosis and related cardiovascular diseases develop with age and are associated with an accumulation of senescent cells. Various genotoxic stresses, such as telomere attrition and oxidative stress induced by metabolic stress, can promote senescence of endothelial cells and vascular smooth muscle cells (ECs and VSMCs, respectively) by upregulating antitumor pathways such as p53/p21 or p16/retinoblastoma Senescent vascular cells exhibit proinflammatory phenotype referred to as a senescence-associated secretory phenotype (SASP), accelerating vascular inflammation, and atherogenesis in these cells. Accumulation of senescent cells also causes altered regenerative capacity of the vascular wall and impaired clearance of plaque deposits, leading to the development of plaque with a thin fibrotic cap. Several studies have indicated that senescence of vascular cells plays an important role in the pathological changes associated with atherosclerosis, which leads to the onset of lethal cardiovascular diseases including: ischemic heart diseases aortic aneurysm, and cerebrovascular diseases. Targeting senescent cells has now become an emerging therapeutic strategy for advanced atherosclerosis in elderly patients. In particular, preclinical studies have shown that senolytic treatment may ameliorate the development and progression of atherosclerosis without increasing the chance of tumorigenesis.