Published Online
on November 13, 2006

A more recent version of this article appeared on November 28, 2006

This Article Full Text (PDF) All Versions of this Article: 114/22/2382    most recent CIRCULATIONAHA.106.640185v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pei, H. Articles by Shi, W. Search for Related Content PubMed PubMed Citation Articles by Pei, H. Articles by Shi, W. Pubmed/NCBI databases Substance via MeSH Related Collections Genetics of cardiovascular disease Lipid and lipoprotein metabolism Mechanism of atherosclerosis/growth factors Animal models of human disease Genetically altered mice

Submitted on May 16, 2006
Revised on August 14, 2006
Accepted on September 22, 2006

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, and 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.

^* To whom correspondence should be addressed. E-mail: ws4v{at}virginia.edu.

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.

Key words: atherosclerosis • endothelium • grafting • transplantation

This article has been cited by other articles:

				Q. Li, Y. Li, Z. Zhang, T. R. Gilbert, A. H. Matsumoto, S. E. Dobrin, and W. Shi Quantitative Trait Locus Analysis of Carotid Atherosclerosis in an Intercross Between C57BL/6 and C3H Apolipoprotein E-Deficient Mice Stroke, January 1, 2008; 39(1): 166 - 173. [Abstract] [Full Text] [PDF]

				S. S. Wang, W. Shi, X. Wang, L. Velky, S. Greenlee, M. T. Wang, T. A. Drake, and A. J. Lusis Mapping, Genetic Isolation, and Characterization of Genetic Loci That Determine Resistance to Atherosclerosis in C3H Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2671 - 2676. [Abstract] [Full Text] [PDF]

				S. M. Schwartz, Z. S. Galis, M. E. Rosenfeld, and E. Falk Plaque Rupture in Humans and Mice Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 705 - 713. [Abstract] [Full Text] [PDF]