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细胞衰老作为心血管疾病的一个可靶向风险因素:治疗意义:家族系列研究

Cellular Senescence as a Targetable Risk Factor for Cardiovascular Diseases: Therapeutic Implications: Family Series.

作者信息

Kumar Manish, Yan Pengyi, Kuchel George A, Xu Ming

机构信息

UConn Center on Aging, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Division of Critical Care Medicine, Montefiore Medical Center, Bronx, New York, USA.

出版信息

JACC Basic Transl Sci. 2024 Apr 8;9(4):522-534. doi: 10.1016/j.jacbts.2023.12.003. eCollection 2024 Apr.

Abstract

The prevalence of cardiovascular diseases markedly rises with age. Cellular senescence, a hallmark of aging, is characterized by irreversible cell cycle arrest and the manifestation of a senescence-associated secretory phenotype, which has emerged as a significant contributor to aging, mortality, and a spectrum of chronic ailments. An increasing body of preclinical and clinical research has established connections between senescence, senescence-associated secretory phenotype, and age-related cardiac and vascular pathologies. This review comprehensively outlines studies delving into the detrimental impact of senescence on various cardiovascular diseases, encompassing systemic atherosclerosis (including coronary artery disease, stroke, and peripheral arterial disease), as well as conditions such as hypertension, congestive heart failure, arrhythmias, and valvular heart diseases. In addition, we have preclinical studies demonstrating the beneficial effects of senolytics-a class of drugs designed to eliminate senescent cells selectively across diverse cardiovascular disease scenarios. Finally, we address knowledge gaps on the influence of senescence on cardiovascular systems and discuss the future trajectory of strategies targeting senescence for cardiovascular diseases.

摘要

心血管疾病的患病率随年龄显著上升。细胞衰老作为衰老的一个标志,其特征在于不可逆的细胞周期停滞以及衰老相关分泌表型的表现,而这已成为导致衰老、死亡以及一系列慢性疾病的一个重要因素。越来越多的临床前和临床研究已经建立了衰老、衰老相关分泌表型与年龄相关的心脏和血管病变之间的联系。本综述全面概述了深入研究衰老对各种心血管疾病有害影响的研究,包括全身性动脉粥样硬化(包括冠状动脉疾病、中风和外周动脉疾病),以及高血压、充血性心力衰竭、心律失常和心脏瓣膜病等病症。此外,我们还有临床前研究证明了衰老细胞溶解剂(一类旨在在各种心血管疾病情况下选择性消除衰老细胞的药物)的有益作用。最后,我们阐述了关于衰老对心血管系统影响方面的知识空白,并讨论了针对心血管疾病的衰老靶向策略的未来发展方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/11055207/5738c029eb84/ga1.jpg

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