DETECTION AND MODULATION OF VULNERABLE ATHEROSCLEROTIC P

$486,581P50FY2005HLNIH

Brigham And Women'S Hospital, Boston MA

Investigators

Linked publications & trials

Paper 26821944 Paper 25092171 Paper 25037606 Paper 23810579 Paper 23771947 Paper 22566565 Paper 22491251 Paper 21868704 Paper 21817099 Paper 21493897 Paper 21412153 Paper 20697023 Paper 19720934 Paper 19153555 Paper 19047056 Paper 19028921 Paper 17932568 Paper 17853943 Paper 17673684 Paper 17673673 Paper 17546038 Paper 17442972 Paper 17404153 Paper 17391676 Paper 17296784 Paper 17082490 Paper 17060381 Paper 17056576 Paper 17038637 Paper 16999225 Paper 16894036 Paper 16801460 Paper 16799196 Paper 16614356 Paper 16585266 Paper 16574902 Paper 16461842 Paper 16385081 Paper 16341264 Paper 16230484 Paper 16203910 Paper 16198835 Paper 15983262 Paper 15982660 Paper 15893173 Paper 15878865 Paper 15861316 Paper 15861315 Paper 15811956 Paper 15718498 Paper 15665085 Paper 15653570 Paper 15466704 Paper 15451791 Paper 15238817 Paper 15197138 Paper 15178558 Paper 15177268 Paper 15152295 Paper 15142860 Paper 15136591 Paper 15113402 Paper 15096453 Paper 15081469 Paper 14695322 Paper 14688302 Paper 14581383 Paper 12810688 Paper 12771009 Paper 12707043 Paper 12645637 Paper 12639996 Paper 12618521 Paper 12615659 Paper 12482832 Paper 12355428 Paper 12234362 Paper 12231565 Paper 12221058 Paper 12188206 Paper 12171797 Paper 12163375 Paper 12081998 Paper 11994507 Paper 11978801 Paper 11978082 Paper 11929779 Paper 11914242 Paper 11877368 Paper 11795264 Paper 11795257 Paper 11753215 Paper 11739273 Paper 11711496 Paper 11696462 Paper 11602491 Paper 11544205 Paper 11490021 Paper 11457759 Paper 11420040

Abstract

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.

View original record on NIH RePORTER →