Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA.
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Cells. 2023 May 2;12(9):1296. doi: 10.3390/cells12091296.
Senescent cell accumulation has been observed in age-associated diseases including cardiovascular diseases. Senescent cells lack proliferative capacity and secrete senescence-associated secretory phenotype (SASP) factors that may cause or worsen many cardiovascular diseases. Therapies targeting senescent cells, especially senolytic drugs that selectively induce senescent cell removal, have been shown to delay, prevent, alleviate, or treat multiple age-associated diseases in preclinical models. Some senolytic clinical trials have already been completed or are underway for a number of diseases and geriatric syndromes. Understanding how cellular senescence affects the various cell types in the cardiovascular system, such as endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells, progenitor cells, and cardiomyocytes, is important to facilitate translation of senotherapeutics into clinical interventions. This review highlights: (1) the characteristics of senescent cells and their involvement in cardiovascular diseases, focusing on the aforementioned cardiovascular cell types, (2) evidence about senolytic drugs and other senotherapeutics, and (3) the future path and clinical potential of senotherapeutics for cardiovascular diseases.
衰老细胞的积累与心血管疾病等与年龄相关的疾病有关。衰老细胞缺乏增殖能力,并分泌衰老相关分泌表型(SASP)因子,这些因子可能导致或加重许多心血管疾病。针对衰老细胞的治疗方法,特别是选择性诱导衰老细胞清除的衰老细胞溶解药物,已在临床前模型中显示出可延缓、预防、减轻或治疗多种与年龄相关的疾病。一些衰老细胞溶解的临床试验已经完成或正在进行,用于多种疾病和老年综合征。了解细胞衰老如何影响心血管系统中的各种细胞类型,如内皮细胞、血管平滑肌细胞、成纤维细胞、免疫细胞、祖细胞和心肌细胞,对于将衰老治疗转化为临床干预措施非常重要。这篇综述强调了:(1)衰老细胞的特征及其在心血管疾病中的作用,重点关注上述心血管细胞类型;(2)衰老细胞溶解药物和其他衰老治疗的证据;(3)衰老治疗在心血管疾病中的未来路径和临床潜力。