Fig. 1: Cardiomyocytes and cardiac nonmyocytes interact with each other within the local microenvironment.
From: Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets
Cardiac nonmyocytes modulate cardiomyocytes by releasing signals, leading to cardiac senescence. Dysfunctional endothelial cells (ECs) release proinflammatory factors (IL-6 and IL-33), Ang II, and ET-1 to promote cardiomyocyte senescence. Fibroblasts induce senescence by producing IL-11, IL-33, and integrin. Immune cells release various signals to regulate cardiomyocyte senescence directly. Reciprocally, senescent dysfunctional cardiomyocytes undergo a senescence-associated secretory phenotype (SASP) to recruit immune cells. Aging cardiomyocytes produce SASP, VEGF, and exosomes to induce senescence in ECs. Similarly, the functional impairment in fibroblasts is regulated by dysfunctional cardiomyocytes through the secretion of IL-6, CCN1, and exosomes.
