Role of Blood-Borne Fibroblast Precursors in Ischemic Cardiomyopathy

血源性成纤维细胞前体在缺血性心肌病中的作用

• 批准号: 8774624
• 负责人: MARK L ENTMAN
• 金额: $ 37.8万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8774624
• 关键词: Aging; Angiotensin II; Area; Blood; C-reactive protein; CCL2 gene; Cardiac; Cardiomyopathies; Cells; Chemotaxis; Chronic; Cicatrix; Data; Deposition; Development; Etiology; Event; Exhibits; Fibroblasts; Fibrosis; Fill-It; Generations; Genetic; Genetic Models; Goals; Grant; Heart; Heart Diseases; Heart failure; Hypertrophy; Immune System Diseases; In Vitro; Infarction; Inflammatory; Infusion procedures; Interleukin-13; Intervention; Ischemia; Lymphocyte; Lymphokines; Mediating; Modeling; Mus; Myelogenous; Myocardial; Myocardial dysfunction; Pathologic; Population; Process; Production; Publishing; Role; Signal Transduction; TNF gene; Therapeutic; Tissues; base; chemokine; coronary fibrosis; data modeling; in vivo; innovation; interstitial; macrophage; migration; monocyte; prevent; receptor; research study; response; therapy design; uptake

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.

描述(申请人提供)：慢性心脏病的主要原因都与心脏中纤维组织的非适应性沉积有关。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。利用反复缺血和血管紧张素II输注的模型，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功能障碍引起的假说，在适当的情况下，免疫和炎症机制是有保护作用的。该提案研究了与特定炎症细胞摄取相关的细胞信号，以及导致特定类型的成纤维细胞产生的机制，该类型的纤维细胞是心脏纤维化的必备因素。我们提供的证据表明，这一机制对于由各种病理原因引起的非适应性心脏纤维化至关重要。该项目的目标是从不同的慢性心脏疾病中确定导致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。