DETECTION AND MODULATION OF VULNERABLE ATHEROSCLEROTIC P

描述(由申请人提供)： 斑块破裂引起的不稳定发作经常出现在 稳定的冠状动脉粥样硬化病程。病理研究表明 确定了易破裂的病变的关键特征(大脂 游泳池、突出的炎症成分和薄的纤维帽)，但常规 包括诊断血管造影术在内的检测未能识别出这些重要的 易损斑块的结构特征。 我们的目标是在动脉粥样硬化兔和人类身上开发和验证高密度脂蛋白。 分辨率血管内磁共振成像以识别组织 动脉粥样硬化斑块的特征。炎性成分中的 斑块将通过使用造影剂来描绘，这些造影剂选择性地 被巨噬细胞摄取(超小的超顺磁性氧化铁颗粒) 或定位于血管通透性增加部位的造影剂 (Gd标记白蛋白)--动脉粥样硬化形成的典型特征。 我们将使用高分辨率血管内磁共振成像来 利用斑块特征及其时程变化来表征斑块特征的变化 将降低胆固醇作为一种行之有效的干预措施。我们将测试 在人类中的假设，以及在兔子中的类似验证，密集的 降胆固醇可迅速改善高危形态计量学 斑块的特性和炎症成分，从而导致 快速稳定。这项工作的未来扩展可能会使用 现在经过验证的技术可以用新的治疗方法来测试类似的假设 假定对动脉粥样硬化病变有直接影响的药物。这些 项目被认为是检查#年影响的必要基石。 人类拥有新的治疗策略。 这些研究提供了新的方法来检测和表征 患者易患动脉粥样硬化病变。这是非常需要的信息 不能用常规血管造影术或其他电流获得 临床检测手段。这项工作应该提供新的机械论见解 并促进治疗策略的开发和评估，以进一步 防止斑块破裂、血栓形成和致命的冠状动脉事件。

DESCRIPTION (provided by applicant): Episodes of instability caused by plaque disruption frequently punctuate the course of stable coronary atherosclerosis. Pathological studies have identified critical features of lesions vulnerable to rupture (large lipid pool, prominent inflammatory component and thin fibrous cap) but routine testing including diagnostic angiography fails to identify these important structural features of vulnerable plaques. We aim to develop and validate in atherosclerotic rabbits and in humans, high resolution intravascular magnetic resonance imaging to identify the tissue characteristics of atherosclerotic plaques. The inflammatory component of the plaques will be delineated by the use of contrast agents that are selectively taken up by macrophages (particles of ultrasmall superparamagnetic iron oxide) or contrast agents that localize to sites of increased vascular permeability (gadolinium-labeled albumin)--classical characteristics of atheroma formation. We will use high resolution intravascular magnetic resonance imaging to characterize changes in plaque features and their time course using cholesterol lowering as a well-established intervention. We will test the hypothesis in humans, with parallel validation in rabbits, that intensive cholesterol-lowering can rapidly improve the high risk morphometric characteristics and the inflammatory component of plaques, thereby leading to rapid stabilization. Future extensions of this work might use the technologies validated now to test similar hypotheses with novel therapeutic agents that have a putative direct effect on atherosclerotic lesions. These projects are considered the necessary cornerstone for examining the effects in humans of new therapeutic strategies. These studies provide novel approaches to detection and characterization 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 and evaluation of therapeutic strategies for further protection from plaque rupture, thrombosis and fatal coronary events.