Vascular endothelial growth factor gene transfer inhibits neointimal macrophage accumulation in hypercholesterolemic rabbits.

Abstract

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.

• Authors: Rohit Khurana, Shahida Shafi, John Martin, Ian Zachary
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 24 Issue 6 Pg. 1074-80 (Jun 2004) ISSN: 1524-4636 [Electronic] United States
• PMID: 15072995 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liposomes
• Vascular Cell Adhesion Molecule-1
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Carotid Stenosis (etiology, pathology, therapy)
• Diet, Atherogenic
• Genetic Therapy
• Hypercholesterolemia (complications)
• Intercellular Adhesion Molecule-1 (biosynthesis, genetics)
• Liposomes
• Macrophages (pathology)
• Male
• Mice
• Neovascularization, Pathologic (etiology)
• Prostheses and Implants
• Rabbits
• Tunica Intima (drug effects, pathology)
• Vascular Cell Adhesion Molecule-1 (biosynthesis, genetics)
• Vascular Endothelial Growth Factor A (genetics)