This study is designed to explore the question whether an atherogenic lipoprotein environment may impair the ability of established arterial channels to grow (circumferential arterial expansion) and new channels to form (neovascularization; new collaterals). The hypothesis is that vascular growth or angiogenesis is dependent upon the integrity of endothelial function which may be impaired in atherosclerosis, a circumstance that could limit angiogenic reserve and aggravate the effects of atheromatous and thrombotic occlusive disease. The hypothesis will be tested in normo- and hypercholesterolemic rabbits with carotid artery occlusion, an intervention that evokes in normal rabbits a predictable flow-dependent hyperplastic vascular growth response demonstrable on the basis of 3H- thymidine incorporation studies. Pilot studies have shown that mechanical de-endothelialization of hypercholesterolemia without endothelial denudation markedly impairs flow-dependent vascular growth. In similar experiments, the central ear artery will be occluded to increase flow through the medial ear artery. These experiments will be performed in parallel in both ears, one ear receiving placebo, the other a putative growth factor such as heparin or basic fibroblast growth factor. The agents will be delivered topically with osmotic micropumps. The research should answer the important question whether impaired tissue perfusion in atherosclerosis can be improved by supplying missing angiogenic factors capable of stimulating compensatory vessel growth.
| Bucay, M; Nguy, J; Barrios, R et al. (1998) Impaired adaptive vascular growth in hypercholesterolemic rabbit. Atherosclerosis 139:243-51 |
| Oraevsky, A A; Jacques, S L; Pettit, G H et al. (1993) XeCl laser ablation of atherosclerotic aorta: luminescence spectroscopy of ablation products. Lasers Surg Med 13:168-78 |
| Oraevsky, A A; Jacques, S L; Pettit, G H et al. (1993) XeCl laser-induced fluorescence of atherosclerotic arteries. Spectral similarities between lipid-rich lesions and peroxidized lipoproteins. Circ Res 72:84-90 |
| Mangin Jr, E L; Kugiyama, K; Nguy, J H et al. (1993) Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta. Circ Res 72:161-6 |
