A. Orlandi et al., Aging influences development and progression of early aortic atherosclerotic lesions in cholesterol-fed rabbits, ART THROM V, 20(4), 2000, pp. 1123-1136
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.