on April 8, 2004
Published online before print April 8, 2004, doi: 10.1161/01.ATV.0000128127.57688.e0
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Submitted on February 13, 2004
Accepted on March 10, 2004
Vascular Endothelial Growth Factor Gene Transfer Inhibits Neointimal Macrophage Accumulation in Hypercholesterolemic Rabbits
Rohit Khurana ;
From BHF Laboratories, Department of Medicine, University College London, United Kingdom.
* To whom correspondence should be addressed. E-mail: I.Zachary{at}ucl.ac.uk.
Objective--This study aims to determine the effects of periadventitial vascular endothelial growth factor (VEGF) gene transfer on neointima formation and macrophage accumulation induced by collar placement around the carotid artery in hypercholesterolemic rabbits.
Methods and Results--Collar placement around the carotid artery in cholesterol-fed rabbits induced intimal thickening with increased neointimal macrophage content. Liposome-mediated VEGF gene transfer, confirmed by transgene-specific RT-PCR, caused a marked inhibition of both intimal thickening and macrophage accumulation compared with a lacZ control gene. VEGF gene transfer was not accompanied by a significant increase in adventitial neovascularization. Collaring of carotid arteries in hypercholesterolemic rabbits also upregulated endothelial VCAM-1 expression. Inhibition of neointimal macrophage infiltration in VEGF-transduced, collared arteries were associated with decreased endothelial VCAM-1.
Conclusions--VEGF gene transfer inhibits collar-induced intimal thickening, macrophage accumulation, and VCAM-1 expression in cholesterol-fed rabbits. These findings support the concept that low-level VEGF expression can exert arterioprotective effects in the presence of high blood cholesterol.
Key words: VCAM • vascular smooth muscle • endothelium • atherosclerosis • collar
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