Research Of Significance And Mechanism Of Pyk₂ In Cardiac Interstitial Fibrosis

Background:Cardiac remodeling is characterized by a structural rearrangement of components of the normal chamber wall that involves cardiomyocyte hypertrophy, cardiac fibroblast proliferation, fibrosis, and cell death. Cardiac fibrosis, which is a disproportionate accumulation of fibrillar collagen, is crucial for the transition of cardiac function from adaptive to maladaptive, cardiac remodeling from reversible to irreversible state.The cardiac fibrosis stiffens the ventricles and impedes both contraction and relaxation. Fibrosis can also impair the electrical coupling of cardiomyocytes by separating myocytes with extracellularmatrix proteins. Furthermore, fibrosis results in reduced capillary densities and an increased oxygen diffusion distance that can lead to hypoxia of myocytes. Thus, fibrosis profoundly affects myocyte metabolism and performance and ultimately ventricular function. Cardiac fibrosis is closely associated with rheumatic heart disease, hypertension, heart failure, cardiac arrhythmia and cardiogenic sudden death, etc.Cardiac fibroblasts play a central role in the maintenance of extracellularmatrix in the normal and pathophysiological heart. Injurious stimuli evoke multiple signaling pathways in cardiac fibroblasts that lead to coordinate and sequential gene regulation. Activated fibroblasts produce extracellularmatrix proteins and proteinases, as well as autocrine and paracrine factors, and mediate cardiac remodeling processes.The activity at transcriptional regulatory regions in cardiac fibrosis is not a collection of activities of individual transcription factors, but instead emerges as a network of synergistic interactions. Therefore, to fully understand the mechanism of cardiac remodeling, we need to investigate the molecular networks that control the activities of cardiac fibroblasts.CFs is the ultimately effect cell in cardiac fibrosis, and serves as mediator of fibrotic myocardial remodeling in the injured and failing heart, it maybe a novel therapeutic target of cardiac...