DETECTION AND MODULATION OF VULNERABLE ATHEROSCLEROTIC P

点击翻译按钮获取中文摘要

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.