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都与心脏纤维组织的非适应性沉积有关。由于纤维组织干扰心功能和心脏充盈，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，本研究旨在探讨心脏非适应性纤维化是由免疫和炎症机制的功能障碍引起的，在适当的情况下，这些机制具有保护作用。该提案研究了与特定炎症细胞摄取相关的细胞信号传导，以及导致特定成纤维细胞类型产生的机制，该类型专为心脏纤维化所必需。我们提供的证据表明，这种机制对由各种病理原因引起的非适应性心脏纤维化至关重要。该项目的目标是确定各种慢性心脏病导致心脏纤维化的共同因素，并提出可能减轻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.