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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1074.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Vascular Endothelial Growth Factor Gene Transfer Inhibits Neointimal Macrophage Accumulation in Hypercholesterolemic Rabbits

Rohit Khurana; Shahida Shafi; John Martin; Ian Zachary

From BHF Laboratories, Department of Medicine, University College London, United Kingdom.

Correspondence to Ian Zachary, BHF Laboratories, Department of Medicine, The Rayne Building, University College London, 5 University Street, London WC1E 6JJ, United Kingdom. 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 was 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.

Periadventitial VEGF gene delivery inhibits intimal thickening, macrophage accumulation, and endothelial VCAM-1 expression induced by collar placement around the carotid artery in hypercholesterolemic rabbits. These findings indicate that VEGF can exert a local arterioprotective effect in the presence of high blood cholesterol.

Key Words: VCAM • vascular smooth muscle • endothelium • atherosclerosis • collar

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