Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Cardiovasc Drugs Ther. 2022 Feb;36(1):187-196. doi: 10.1007/s10557-020-07075-w. Epub 2020 Sep 26.
Ageing is the biggest risk factor for impaired cardiovascular health, with cardiovascular disease being the leading cause of death in 40% of individuals over 65 years old. Ageing is associated with both an increased prevalence of cardiovascular disease including heart failure, coronary artery disease, and myocardial infarction. Furthermore, ageing is associated with a poorer prognosis to these diseases. Genetic models allowing the elimination of senescent cells revealed that an accumulation of senescence contributes to the pathophysiology of cardiovascular ageing and promotes the progression of cardiovascular disease through the expression of a proinflammatory and profibrotic senescence-associated secretory phenotype. These studies have resulted in an effort to identify pharmacological therapeutics that enable the specific elimination of senescent cells through apoptosis induction. These senescent cell apoptosis-inducing compounds are termed senolytics and their potential to ameliorate age-associated cardiovascular disease is the focus of this review.
衰老是心血管健康受损的最大风险因素,40%的 65 岁以上人群的主要死因是心血管疾病。衰老与包括心力衰竭、冠状动脉疾病和心肌梗死在内的心血管疾病的患病率增加有关。此外,衰老与这些疾病的预后较差有关。允许消除衰老细胞的遗传模型表明,衰老细胞的积累有助于心血管衰老的病理生理学,并通过表达促炎和促纤维化的衰老相关分泌表型促进心血管疾病的进展。这些研究促使人们努力寻找通过诱导细胞凋亡来特异性消除衰老细胞的药理学治疗方法。这些诱导衰老细胞凋亡的化合物被称为衰老细胞清除剂,它们改善与年龄相关的心血管疾病的潜力是本综述的重点。