DETECTION AND MODULATION OF VULNERABLE ATHEROSCLEROTIC P

易损动脉粥样硬化 P 的检测和调节

• 批准号: 7056679
• 负责人: PETER GANZ
• 金额: $ 48.66万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056679
• 关键词: angiocardioultrasonography; angiography; antihypercholesterolemic agent; atherosclerotic plaque; bioimaging /biomedical imaging; cardiovascular disorder diagnosis; cholesterol; contrast media; coronary artery; diagnosis design /evaluation; dietary lipid; human subject; laboratory rabbit; macrophage; magnetic resonance imaging; nonhuman therapy evaluation; nutrition related tag; pathologic process; patient oriented research; vascular endothelium; vascular endothelium permeability

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.

描述（由申请人提供）： 斑块破裂引起的不稳定性发作经常打断 稳定性冠状动脉粥样硬化过程。病理学研究 确定了易破裂病变的关键特征（大脂质 池，突出的炎症成分和薄的纤维帽），但常规 包括诊断性血管造影术在内的测试无法识别这些重要的 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中开发和验证， 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， 斑块将通过使用造影剂来描绘 被巨噬细胞（超小超顺磁性氧化铁颗粒）吸收 或定位于血管渗透性增加的部位的造影剂 （钆标记白蛋白）--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， 表征斑块特征的变化及其时间进程， 降低胆固醇是一种行之有效的干预措施。我们将测试 假设在人类中，与兔子平行验证， 降低胆固醇可以迅速改善高风险的形态计量学 特征和斑块的炎症成分，从而导致 快速稳定。此工作的未来扩展可能会使用 现在验证的技术可以用新的治疗方法来测试类似的假设 对动脉粥样硬化病变具有推定的直接作用的药剂。这些 项目被认为是审查影响的必要基石， 新的治疗策略。 这些研究提供了新的方法来检测和表征 易受动脉粥样硬化损害的患者。这些急需的信息 不能用常规血管造影术或其他电流获得 临床试验方法。这项工作应该提供新的机械见解 并促进治疗策略的开发和评估， 防止斑块破裂、血栓形成和致命的冠状动脉事件。