miR-33 Regulation of Adaptive Fibrotic Response in Cardiac Remodeling

摘要: Despite substantial improvements in prevention, diagnosis, and therapeutic strategies, cardiovascular diseases remain the leading cause of mortality morbidity worldwide. Cardiac fibrosis, a critical hallmark maladaptive hypertrophy heart failure (HF), is characterized by excessive uncontrolled accumulation extracellular matrix (ECM) cardiac fibroblasts (CFs) interstitial perivascular space.1 CFs, primarily embryonic epicardial endothelial origins,2 are predominant noncardiomyocyte population, accounting for 20% total cell population adult murine heart.3 In addition to their traditional functions regulating ECM synthesis metabolism controlling remodeling, scar formation, tissue repair, CFs serve as functionally pluralistic cells involved inflammatory responses, cardiomyocyte survival, vasculogenesis.4,5 Article, see p 835 In heart, present quiescent state with low proliferative capacity responsible homeostasis, providing structural scaffold cardiomyocytes. also express gap junction protein connexin-43, which mediates electric coupling cardiomyocytes CFs.6 The mammalian has limited regenerative after pathological injury. repair wounds consists removal dead replacement myocytes loss collagen-based fibrotic preserve myocardial integrity function. importance remodeling wound healing been extensively studied involves all 3 phases process: acute response, proliferation, late maturation. After an injury, release proinflammatory cytokines, promote own proliferation feed-forward loop trigger differentiation into myofibroblast phenotype. This hyperproliferative type secretes high levels profibrotic factors proteins. adaptive fibrosis can maintain prevent injured from dysfunction rupture; …