Expression of vascular cell adhesion molecule-1 (VCAM-1) in the aortae of hypercholesterolemic rabbits with high (HAR) and low (LAR) atherosclerotic response.

Recently we have described two strains of rabbits, one with a low (LAR) the other with a high (HAR) atherosclerotic response to dietary hypercholesterolemia. After feeding a cholesterol diet for 12 weeks, HAR rabbits developed atherosclerotic lesions throughout the entire aortic arch and thoracic aorta. In contrast, the lesions in LAR rabbits were mainly confined to the aortic arch. Presently we studied the cellular composition and expression of vascular cell adhesion molecule-1 (VCAM-1) in aortic lesions and in the uninvolved aorta of cholesterol fed HAR and LAR rabbits. Plasma cholesterol levels were 1106 +/- 160 and 1152 +/- 232 mg/dl in HAR and LAR rabbits, respectively, and the distribution of cholesterol among the lipoprotein fractions was similar after 16 weeks of 0.5% cholesterol feeding. In analogy to our previous findings, in the HAR rabbits more than 70% of the aorta (aortic arch and thoracic aorta) was covered with lesions, whereas in the LAR rabbits the lesions were seen in the aortic arch only and covered less than 20% of the total aortic surface. The cellular composition of aortic lesions was defined using specific antibodies to macrophages, smooth muscle cells, T lymphocytes and Ia expressing cells. All these cellular elements were represented in lesions derived from both strains of rabbits. We also examined the expression of VCAM-1 in the aorta of HAR and LAR rabbits after cholesterol feeding. In the aortic arch, a positive reaction for VCAM-1 was found in lesions from both strains of rabbits. The staining was seen in the endothelium and within the lesion, mainly at its base. In the thoracic aorta of HAR rabbits, VCAM-1 expression was found in all lesions examined. In the thoracic aorta of LAR rabbits, VCAM-1 expression was seen in an occasional very small lesion found at the ostium of an intercostal artery. These results show that the VCAM-1 gene is expressed in the LAR rabbits, but its induction is perhaps attenuated.