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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:238.)
© 2001 American Heart Association, Inc.

Vascular Biology

Vascular Cell Adhesion Molecule-1 Augments Adenovirus-Mediated Gene Transfer

Yi Chu; Donald D. Heistad; Myron I. Cybulsky; Beverly L. Davidson

From the Departments of Internal Medicine (Y.C., D.D.H., B.L.D.), Neurology (B.L.D.), and Pharmacology (D.D.H.), the Cardiovascular Center (D.D.H.), the Center on Aging (D.D.H.), and the Program in Gene Therapy (D.D.H., B.L.D.), University of Iowa College of Medicine, Iowa City; the Veterans Administration Medical Center (D.D.H.), Iowa City, Iowa; and the Department of Laboratory Medicine and Pathobiology (M.I.C.), The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada.

Correspondence to Beverly L. Davidson, PhD, Roy J. Carver Associate Professor in Internal Medicine and Neurology, Director, Gene Transfer Vector Core, University of Iowa College of Medicine, Iowa City, IA 52242. E-mail beverly-davidson{at}uiowa.edu

Abstract—We have reported that adenovirus-mediated gene transfer is augmented in the endothelium of atherosclerotic blood vessels. We observed that vascular cell adhesion molecule-1 (VCAM-1) shares some homology with the coxsackievirus and adenovirus receptor. Because VCAM-1 is upregulated on atherosclerotic endothelial cells, we hypothesized that VCAM-1 may act as an auxiliary receptor to augment adenovirus-mediated gene transfer. To test this hypothesis, stable NIH 3T3 cell lines that constitutively express VCAM-1 on the cell surface were generated. Recombinant adenovirus 5 (Ad5), which contains the reporter ß-galactosidase gene, was used to compare Ad5 infection in VCAM-1⁺ and parental NIH 3T3 cells. Total ß-galactosidase activity and the number of transgene-positive cells were 6- to 10-fold and 5-fold higher, respectively, in VCAM-1⁺ than in VCAM-1^- cells. Ad5 binding to VCAM-1⁺ cells was increased by 3-fold over VCAM-1^- cells. Soluble VCAM-1 protein, present during infection or viral binding, reduced ß-galactosidase activity in VCAM-1⁺ cells in a dose-dependent manner. Taken together, we conclude that VCAM-1 can mediate adenovirus binding and infection. This may explain, in part, the previous finding that adenovirus-mediated gene transfer is augmented in atherosclerotic arteries.

Key Words: vascular cell adhesion molecule-1 • coxsackie and adenovirus receptor • adenovirus-mediated gene transfer • atherosclerosis

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