Role of Blood-Borne Fibroblast Precursors in Ischemic Cardiomyopathy

描述（由申请人提供）：慢性心脏病的主要原因均与心脏中纤维组织的非适应性存款有关。由于纤维组织干扰心脏功能和心脏充盈，它是心力衰竭的主要原因。利用重复缺血和血管紧张素II输注模型，本提案旨在研究心脏非适应性纤维化源于免疫和炎症机制功能障碍的假设，在适当的情况下，免疫和炎症机制是保护性的。该提案研究了与特定炎性细胞的摄取相关的细胞信号传导以及导致产生特定成纤维细胞类型的机制，该成纤维细胞类型对心脏纤维化是专性的。我们提供的证据表明，这种机制是至关重要的非适应性心脏纤维化所造成的各种病理原因。该项目的目标是确定导致不同慢性心脏病心脏纤维化的共同因素，并提出可能缓解这一过程的潜在干预措施。

DESCRIPTION (provided by applicant): The leading causes of chronic heart disease are all associated with a non-adaptive deposit of fibrous tissue in the heart. Since fibrous tissue interferes with both cardiac function and cardiac filling, it is a major cause of heart failure. Utilizing models of repetitive ischemia and angiotensin II infusion, this proposal intends to investigate the hypothesis that non-adaptive fibrosis of the heart arises from dysfunction of the immune and inflammatory mechanisms, which, under appropriate circumstances, are protective. The proposal studies the cell signaling associated with the uptake of specific inflammatory cells and the mechanisms by which this results in the generation of a specific fibroblast type that is obligate for cardiac fibrosis. We provide evidence that this mechanism is critical to non-adaptive cardiac fibrosis resulting from a variety of pathological causes. The goal of the project is to identify the common factors leading to cardiac fibrosis from diverse chronic cardiac conditions and suggest potential interventions which might mitigate this process.