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

Article

关键词: CIRCULATING ADHESION MOLECULES;    DEFICIENT MOUSE STRAINS;    APOLIPOPROTEIN-E;    ENDOTHELIAL-CELLS;    MICE;    HYPERCHOLESTEROLEMIA;    LESIONS;    LIPOPROTEINS;    INFLAMMATION;    CHOLESTEROL;   

DOI  :  10.1161/CIRCULATIONAHA.106.640185

来源: SCIE

【 摘 要 】

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 (44983 +/- 11702 versus 5600 +/- 4885 mu m(2) 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.

【 授权许可】

Free