Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
Department of Pharmacy, Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, PR China.
Biochim Biophys Acta Mol Basis Dis. 2019 Jul 1;1865(7):1810-1821. doi: 10.1016/j.bbadis.2018.08.015. Epub 2018 Aug 16.
Aging is a worldwide challenge, and it is accompanied by the accumulation of senescent cells. Cellular senescence is traditionally defined as permanent cell growth arrest and currently includes the senescence-associated secretory phenotype (SASP). There are two main types of cellular senescence, including telomere-dependent replicative senescence and stress-induced premature senescence. The process of cellular senescence is mainly controlled by two effector pathways, namely, the p53-p21 and p16-retinoblastoma protein (pRB) pathways. Vascular smooth muscle cells (VSMCs) are integral parts of arteries and play an important role in vascular structure and function. VSMC senescence may be triggered by many factors, such as angiotensin II, oxidative stress, inflammation, DNA damage, and small molecule compounds. These inducers are able to genetically and epigenetically regulate VSMC senescence. The senescence of VSMCs together with the SASP contributes to chronic vascular inflammation, the loss of arterial function, and the development of age-related diseases. Current evidence suggests that the senescence of VSMCs might be harmful to individual health, whereas its influence on the lifespan is not clear. The purpose of this paper was to review the current knowledge regarding VSMC senescence and its relevance to hypertension, atherosclerosis, and diabetes, as well as the potential mechanisms responsible for VSMC senescence in these age-related diseases.
衰老是一个全球性的挑战，伴随着衰老细胞的积累。细胞衰老传统上被定义为细胞生长的永久停滞，目前包括衰老相关分泌表型（SASP）。细胞衰老有两种主要类型，包括端粒依赖性复制性衰老和应激诱导的早衰。细胞衰老的过程主要受两条效应途径的控制，即 p53-p21 和 p16-Rb 途径。血管平滑肌细胞（VSMC）是动脉的重要组成部分，在血管结构和功能中发挥重要作用。血管平滑肌细胞衰老可能由多种因素触发，如血管紧张素 II、氧化应激、炎症、DNA 损伤和小分子化合物。这些诱导剂能够在基因和表观遗传水平上调节 VSMC 衰老。VSMC 衰老和 SASP 共同导致慢性血管炎症、动脉功能丧失和与年龄相关的疾病的发展。目前的证据表明，VSMC 的衰老可能对个体健康有害，但其对寿命的影响尚不清楚。本文旨在综述目前关于 VSMC 衰老及其与高血压、动脉粥样硬化和糖尿病的相关性的知识，以及这些与年龄相关的疾病中导致 VSMC 衰老的潜在机制。
