Effect of aging on aortic expression of the vascular cell adhesion molecule-1 and atherosclerosis in murine models of atherosclerosis

Although age is a strong risk factor for atherosclerosis, it is unclear whe ther age may directly influence the process of atherogenesis. We, therefore , performed several studies in young (2-4 months old), mature (10-14 months old), and old (20-23 months old) mice to determine if the rate of aortic l esion formation increases with age, and whether this is related to Increase s in oxidative stress or vascular cell adhesion molecule (VCAM-1) expressio n in the aortic wall. In chow-fed low-density lipoprotein receptor-deficien t (LDLR-/-) mice, plasma total cholesterol levels increased with age (250 /- 52 mg/dl in young, 276 +/- 58 in mature, and 314 +/- 101 mg/dl in old mi ce), In contrast, the extent of atherosclerosis rose more rapidly, increasi ng from 3.6 +/- 2.7% of the aortic surface in mature mice to 18.2 +/- 8% in old mice. Plasma and tissue levels of antioxidant enzymes and molecules, a s well as plasma thiobarbituric acid reactive substances and low-density li poprotein susceptibility to oxidation, did not change with age. In a second study, VCAM-1 expression in the aortic arch and the extent of atherosclero sis in the aortic origin were significantly greater in old LDLR-/- mice tha n in young LDLR-/- mice. Additionally, after 1 month of a high-fat diet, wh ich induced equally elevated plasma cholesterol levels In both young and ol d LDLR-/- mice, VCAM-1 expression and aortic lesion formation were still gr eater in old mice. The extent of atherosclerosis correlated well (r = .65, p < .01) with the expression of VCAM-1 in the aortic origin. In a Anal stud y, we measured VCAM-1 expression and atherosclerosis in young, mature, and old C57BL/6 mice, which have low plasma cholesterol levels (less than or eq ual to 100 mg/dl) when fed a standard chow diet. Although plasma cholestero l levels did not increase with age, old C57BL/6 mice had significantly more VCAM-1 expression in the aortic arch than did young mice. However, no lesi ons were observed in the aortic origin in either group. These data demonstr ate that plasma cholesterol levels and VCAM-1 expression increase with age and suggest that this may contribute to the increased rate of atherosclerot ic lesion formation in LDLR-/- mice. Importantly, the age-dependent increas e in VCAM-1 expression does not appear to be related to plasma cholesterol levels. This study also suggests that in the absence of elevated plasma cho lesterol, an increased expression of VCAM-1 alone is not sufficient for les ion formation.