CHOLESTEROL & PLAQUE RUPTURE--WOMEN AND PLAQUE EROSION

胆固醇

• 批准号: 6078049
• 负责人: Renu Virmani
• 金额: $ 18万
• 依托单位: AMERICAN REGISTRY OF PATHOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6078049
• 关键词: age difference; atherosclerotic plaque; blood vessels; cholesterol; clinical research; collagen; cooperative study; estrogens; female; hemorrhage; hormone regulation /control mechanism; human tissue; immunocytochemistry; macrophage; menstrual cycle; metalloendopeptidases; necrosis; pathologic process; peptidoglycan; plasminogen activator; protein localization; transforming growth factors; women's health; age difference; atherosclerotic plaque; blood vessels; cholesterol; clinical research; collagen; cooperative study; estrogens; female; hemorrhage; hormone regulation /control mechanism; human tissue; immunocytochemistry; macrophage; menstrual cycle; metalloendopeptidases; necrosis; pathologic process; peptidoglycan; plasminogen activator; protein localization; transforming growth factors; women's health

Plaque rupture and plaque erosion are distinct forms of plaque disruption in relation to their morphology association with risk factors, and sex predisposition. Base don recent morphologic studies from our laboratory, we hypothesize that increased cholesterol deposition in plaques that rupture is derived from RBC membranes from recurrent hemorrhage of ruptured vasa vasorum. This in turn leads to a larger necrotic core size and higher macrophage recruitment, features of vulnerable plaques. In contrast, plaque erosion occurs in plaques that have a rich smooth muscle cell base within a proteoglycan matrix. The higher proteoglycan content correlates with the presence of TGF-beta. We postulate that although estrogen inhibits the formation of large lipid- rich plaques, it does not prevent plaque erosion in the presence of TGF- beta. The specific aims of the proposal are (a) to establish the relationship between vasorum and plaque hemorrhage; (b) to establish the association between plaque hemorrhage and necrotic core, and nature of cholesterol within the plaque; (c) to establish the association between plaque hemorrhage and activation of macrophages, expression of MMPs, plasminogen activators, and type of collagen deposition; and (d) to establish the association of plaque erosion with the estrus cycle in women less than 50 years of age, the extent and cells producing TGF-beta and PAI-1, and the identification of collagen proteoglycan matrix. Project 1 will work closely with Project 2 and will be responsible for providing the specimens for molecular analysis and immunohistochemical staining for the study of apoptosis. In addition, analysis of plaque morphology in the animal model proposed in Project 4 will be carried out in project 1.

牙菌斑破裂和斑块侵蚀是斑块破坏的不同形式 关于它们与危险因素和性别的形态关联 倾向。基础DON最近来自我们实验室的形态学研究 我们假设斑块中胆固醇沉积增加了 破裂源自RBC膜的反复出血 破裂的瓦萨·瓦萨鲁姆（Vasa Vasorum）。这反过来导致更大的坏死核心大小 以及更高的巨噬细胞招募，易受攻击的斑块。在 对比，斑块侵蚀发生在具有丰富平滑肌的斑块中 蛋白聚糖基质中的细胞基础。 较高的蛋白聚糖含量与TGF-β的存在相关。 我们假设雌激素抑制了大脂质的形成 丰富的斑块，它不能防止在TGF-存在下斑块侵蚀 beta。该提案的具体目的是（a）建立 血管和斑块出血之间的关系； （b）建立 斑块出血与坏死核之间的关联以及 斑块内的胆固醇； （c）建立关联 斑块出血和巨噬细胞的激活，MMP的表达， 纤溶酶原激活剂和胶原沉积的类型； （d）到 建立妇女的斑块侵蚀与发情周期的关联 不到50岁的年龄，产生TGF-beta的程度和细胞 PAI-1和胶原蛋白蛋白聚糖基质的鉴定。项目1 将与项目2紧密合作，并将负责提供 用于分子分析和免疫组织化学染色的标本 凋亡研究。此外，分析斑块形态 项目4中提出的动物模型将在项目1中进行。