Direct evidence for a crucial role of the arterial wall in control of atherosclerosis susceptibility.
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.


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 microm2 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.
Pei
Hong
H
Department of Radiology, University of Virginia, Charlottesville, VA, USA.
Wang
Yinong
Y
Miyoshi
Toru
T
Zhang
Zhimin
Z
Matsumoto
Alan H
AH
Helm
Gregory A
GA
Tellides
George
G
Shi
Weibin
W
D000818:Animals; D001013:Aorta, Thoracic / Q000033:anatomy & histology* / Q000637:transplantation*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D008055:Lipids / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D001057:Apolipoproteins E; D008055:Lipids; D019010:Vascular Cell Adhesion Molecule-1