Therapeutic opportunities for senolysis in cardiovascular disease

Abstract

Cellular senescence within the cardiovascular system has, until recently, been understudied and unappreciated as a factor in the development of age‐related cardiovascular diseases such as heart failure, myocardial infarction and atherosclerosis. This is in part due to challenges with defining senescence within post‐mitotic cells such as cardiomyocytes. However, recent evidence has demonstrated senescent‐like changes, including a senescence‐associated secretory phenotype (SASP), in cardiomyocytes in response to ageing and cell stress. Other replicating cells, including fibroblasts and vascular smooth muscle cells, within the cardiovascular system have also been shown to undergo senescence and contribute to disease pathogenesis. These findings coupled with the emergence of senolytic therapies, to target and eliminate senescent cells, have provided fascinating new avenues for management of several age‐related cardiovascular diseases with high prevalence. In this review, we discuss the role of senescent cells within the cardiovascular system and highlight the contribution of senescence cells to common cardiovascular diseases. We discuss the emerging role for senolytics in cardiovascular disease management while highlighting important aspects of senescence biology which must be clarified before the potential of senolytics can be fully realized.

Abstract

Cellular senescence and the senescence‐associated secretory phenotype (SASP) have increasingly been recognized as key contributors to multiple cardiovascular diseases. The emergence of senolytic therapies provide intriguing opportunities within the cardiovascular system to arrest or reverse diseases including atherosclerosis, heart failure and pulmonary hypertension. This review aims to improve the understanding of the (patho)physiological roles of senescence in the cardiovascular system to guide safe and effective use of these novel, powerful senolytic therapies.