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(Circulation. 2006;114:2382-2389.)
© 2006 American Heart Association, Inc.

Vascular Medicine

Direct Evidence for a Crucial Role of the Arterial Wall in Control of Atherosclerosis Susceptibility

Hong Pei, MD^*; Yinong Wang, MD, PhD^*; Toru Miyoshi, MD^*; Zhimin Zhang, MD; Alan H. Matsumoto, MD; Gregory A. Helm, MD, PhD; George Tellides, MD, PhD; Weibin Shi, MD, PhD

From the Departments of Radiology (H.P., T.M., A.H.M., Z.Z., W.S.) and Neurosurgery (G.A.H.) and the Cardiovascular Research Center (H.P., T.M., Z.Z., W.S.), University of Virginia, Charlottesville, and Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine and Department of Surgery (Y.W., G.T.), Yale University School of Medicine, New Haven, Conn.

Correspondence to Weibin Shi, University of Virginia, MR4 Room 1171, Box 801339, 409 Lane Rd, Charlottesville, VA 22908. E-mail ws4v{at}virginia.edu

Received May 16, 2006; revision received August 14, 2006; accepted September 22, 2006.

Background— Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit marked differences in atherosclerosis susceptibility. We sought to determine whether the difference in atherosclerosis susceptibility resides at the level of arterial walls.

Methods and Results— Thoracic aortic segments from 8-week-old female B6 and C3H apolipoprotein E–deficient mice were transplanted into the infrarenal aorta of 10-week-old female F1 mice. After transplantation, recipients were maintained on a chow diet for 16 weeks. The donor aortic segments of B6 mice developed significantly larger atherosclerotic lesions than those of C3H (44 983±11 702 versus 5600±4885 µm² per section; P=0.011). Expression of vascular cell adhesion molecule (VCAM)-1 by endothelial cells was examined both in vitro and in vivo. B6 mice expressed significantly more VCAM-1 than their C3H counterparts. Sequence analysis of VCAM-1 cDNA revealed a nucleotide difference in the coding region that resulted in substitution of an amino acid in the protein product.

Conclusions— These data provide direct proof that factors operating in the vessel wall, particularly endothelial cells, can serve as atherosclerosis modifiers and suggest a possibility for the contribution of VCAM-1 to atherosclerosis susceptibility.

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