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

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.

斑块破裂和斑块侵蚀是斑块破裂的不同形式 其形态与危险因素和性别的关系 易感性基于我们实验室最近的形态学研究， 我们假设增加斑块中的胆固醇沉积， 破裂是由反复出血的红细胞膜引起的， 血管破裂这反过来又导致更大的坏死核心尺寸 和更高的巨噬细胞募集，脆弱斑块的特征。在 相反，斑块侵蚀发生在具有丰富平滑肌的斑块中， 蛋白多糖基质内的细胞基底。 较高的蛋白聚糖含量与TGF-β的存在相关。 我们假设，虽然雌激素抑制大脂质的形成- 丰富的斑块，它不能防止在TGF-β存在下的斑块侵蚀。 β的建议的具体目标是：（a）建立 （B）建立血管扩张和斑块出血之间的关系; 斑块出血和坏死核心之间的关联，以及 （c）确定斑块内的胆固醇; 斑块出血和巨噬细胞活化，MMPs表达， 纤溶酶原激活剂和胶原沉积类型;和（d） 建立斑块侵蚀与女性发情周期的关联 小于50岁，产生TGF-β的程度和细胞， 派-1、胶原蛋白多糖基质的鉴定。项目1 将与项目2密切合作，并负责提供 用于分子分析和免疫组织化学染色的标本， 凋亡的研究。此外，分析了牙菌斑的形态， 项目4中提出的动物模型将在项目1中进行。