? For decades, the association of angiogenesis and atherosclerosis has been well known. Expansion of the network of small capillaries that perfuse the wall of larger blood vessels, the vasa vasorum, is recognized in diseases of chronic inflammation (e.g., atherosclerosis) and injury (e.g., angioplasty). Many hypothesize that the inward penetration of neo-vasculature within the arterial wall promotes plaque growth, intra-plaque hemorrhage, and lesion instability. This cascade of events precipitates intra-luminal thrombosis and thromboembolism, which are the proximate causes of myocardial infarction and stroke. Thus, plaque angiogenesis may be the linchpin pathology for the acute complications of atherosclerosis. ? ? The ultimate aims of this proposal involve magnetic resonance molecular imaging of plaque neo-vasculature in conjunction with local anti-angiogenesis therapy. Specifically, alpha v beta 3 -targeted paramagnetic nanoparticles will be used to spatially localize and quantify early atherosclerotic burdens in hyperlipidemic New Zealand White rabbits and to deliver fumagillin to elicit a marked antiangiogenic effect. The project will explore the potential of HMG-Coa reductase inhibitors to sustain the acute """"""""atherolytic"""""""" response of targeted fumagillin therapy and will evaluate the safety, pharmacokinetics and pharmacodynamics of this technology. This novel application of molecular imaging and targeted drug delivery could serve as part of a primary prevention strategy to diagnose, treat, and monitor early atherosclerosis. ? ? ?
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