DETECTION AND MODULATION OF THE VULNERABLE ATHEROSCLEROTIC PLAQUE

易损动脉粥样硬化斑块的检测和调节

• 批准号: 6242761
• 负责人: PETER GANZ
• 金额: $ 33.86万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-23 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6242761
• 关键词: angiocardioultrasonography; atherosclerosis; atherosclerotic plaque; cholesterol; clinical research; coronary artery; dietary lipid; disease /disorder model; human subject; laboratory rabbit; magnetic resonance imaging; nutrition related tag; pathologic process; vascular endothelium

Episodes of instability caused by plaque disruption often punctuate the course of coronary atherosclerosis. Pathological studies have identified critical features of lesions vulnerable to rupture (thin fibrous cap, large lipid pool, prominent inflammatory component) but routine clinical testing including diagnostic angiography fails to identify structural features of vulnerable plaques. Specific Aim 1 aims to develop and validate in rabbits with experimental atherosclerosis high resolution magnetic resonance imaging to identify systematically the features of vulnerable plaques and to follow changes and possible improvements in these features with cholesterol lowering. In addition, we will test the hypothesis that lipid lowering improves overexpression of matrix degrading proteinases in the rabbit atheroma, enzymes which accumulate at locations of the human atherosclerotic lesions prone to rupture. In Specific Aim 2 intravascular ultrasound will be used in patients undergoing cardiac catheterization to examine systematically a) the relationship between intimal growth, compensatory enlargement and lumen size in atherosclerotic lesions and, b) differences in distensibility between normal and diseased coronary segments. Such disparities in distensibility may alter the stress-stain balances within an atherosclerotic lesion, shifting stresses to regions predisposed to rupture. Once again, cholesterol lowering therapy will be used in serial studies to learn which features of the vulnerable plaque improve and need to be monitored when treating patients. These studies may also disclose hitherto unexplored mechanisms whereby cholesterol lowering can promote plaque stability. These studies provide novel approaches to detection of vulnerable atherosclerotic lesions in patients. This much needed information cannot be obtained with conventional angiography or with other current clinical means of testing. This work should provide new mechanistic insights and promote development of therapeutic strategies for further protection from plaque rupture, thrombosis and fatal coronary events.

斑块破裂引起的不稳定发作经常出现 冠状动脉粥样硬化的病程。病理研究表明 确定了易破裂(薄)病变的关键特征 纤维帽、大的脂池、突出的炎症成分) 但包括诊断血管造影术在内的常规临床测试并不能 识别易损斑块的结构特征。具体目标1 目的是在实验性兔身上开发和验证 动脉粥样硬化高分辨率磁共振成像 系统地识别易损斑块的特征，并 跟踪这些功能中的更改和可能的改进 降胆固醇。此外，我们还将检验以下假设 降脂改善基质降解蛋白的过度表达 兔动脉粥样硬化中的蛋白水解酶 人体动脉粥样硬化病变部位易破裂。在……里面 特定目标2血管内超声将用于患者 进行心导管术以系统检查a) 血管内膜生长、代偿性增大与血管病变的关系 动脉粥样硬化病变的管腔大小以及，b) 正常和病变冠状动脉节段之间的扩张性。 这种膨胀性的差异可能会改变应力-应变平衡。 在动脉粥样硬化病变内，将压力转移到区域 易破裂的易破裂的再一次，降胆固醇疗法 将在系列研究中使用以了解 易损斑块改善，治疗时需要监测 病人。这些研究还可能揭示迄今未被探索的 降胆固醇促进斑块形成的机制 稳定性。这些研究提供了新的方法来检测 患者易患动脉粥样硬化病变。这是我们迫切需要的 常规血管造影术无法获得信息或 与其他目前的临床检测手段相结合。这项工作应该是 提供新的机制见解，推动 进一步预防斑块破裂的治疗策略， 血栓形成和致命的冠状动脉事件。