Increased early atherogenesis in young versus old hypercholesterolemic rabbits by a mechanism independent of arterial cell proliferation.

We sought to determine the relative importance of aging and hypercholesterolemia on atherosclerosis. Although plasma cholesterol levels increased similarly in young and old rabbits fed an atherogenic diet for 2 months, aortic atherosclerotic lesions were more prominent in young animals. This finding was associated with an age-dependent reduction in the DNA-binding activity of the proinflammatory nuclear factor kappaB (NF-kappaB) in aortic tissue. Atherosclerotic lesions consisted mostly of macrophages, which displayed a similar proliferative response in both age groups. Independently of the age, medial cell proliferation was low and increased as a function of intimal lesion size. Thus, higher atherogenicity in young rabbits exposed to extreme hypercholesterolemia compared to old counterparts is associated with higher activity of NF-kappaB in the juvenile vessel wall without apparent age-dependent changes in arterial cell proliferation.