Aging influences development and progression of early aortic atherosclerotic lesions in cholesterol-fed rabbits

The arterial wall in aged animals shows an increased susceptibility to deve lop atherosclerotic lesions, although the mechanisms by which aging acts ar e still unclear. We investigated early aortic lesions in aged rabbits (5 to 6 years old, AH group) and young rabbits (2 months old,YH group) after 2 m onths of 0.2% cholesterol feeding. Fatty streaks or spots mainly in the pro ximal segments occupied a relative surface area that was greater in AH than in YH rabbits, although plasma cholesterol and lipoprotein levels did not differ. YH lesions showed an irregular endothelial profile mainly from accu mulations of large, rounded, RAM 11-positive macrophagic foam cells. There was a higher percentage of myocytic, CD-5-positive, proliferating, and term inal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-p ositive cells and larger accumulation of glycosaminoglycans in AH fatty str eaks than in YH lesions. Ligation-mediated polymerase chain reaction confir med differences in apoptosis. Early fibromuscular coats and subendothelial plasma-like insudate were also observed in AH lesions. Aged-matched normoch olesterolemic rabbits showed a diffuse aortic intimal thickening composed o f myocytic cells with a synthetic phenotype and extracellular matrix rich i n glycosaminoglycans. In addition, in aged rabbits, we observed a spontaneo us increase of monocytes adhering to the endothelial surface and a reduced expression of endothelial: nitric oxide synthase in areas distant from the branches. These plasma cholesterol-independent spontaneous changes in the a ortic wall of aged rabbits seem to act as a multiple atherogenic risk facto r. Moreover, age-related differences in the distribution, composition, and proliferative and apoptotic rates represent crucial events during the progr ession of early fatty streaks to advanced plaques.