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

Abstract:

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 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.

journal_name

Circulation

journal_title

Circulation

authors

Pei H,Wang Y,Miyoshi T,Zhang Z,Matsumoto AH,Helm GA,Tellides G,Shi W

doi

10.1161/CIRCULATIONAHA.106.640185

subject

Has Abstract

pub_date

2006-11-28 00:00:00

pages

2382-9

issue

22

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.106.640185

journal_volume

114

pub_type

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