Age-related effects on atherogenesis and scavenger enzymes of intracranialand extracranial arteries in men without classic risk factors for atherosclerosis
Fp. D'Armiento et al., Age-related effects on atherogenesis and scavenger enzymes of intracranialand extracranial arteries in men without classic risk factors for atherosclerosis, STROKE, 32(11), 2001, pp. 2472-2478
Background and Purpose-Atherosclerosis occurs later and is less extensive i
n intracranial arteries than in extracranial arteries. However, the mechani
sms responsible are poorly understood. A previous study has suggested a bet
ter antioxidant protection of intracranial arteries.
Methods-To assess the influence of age on arterial activity of antioxidant
enzymes and atherogenesis, we compared intracranial and extracranial arteri
es of humans of different ages who retrospectively lacked confounding class
ic risk factors (48 premature fetuses aged 6.4 +/-0.8 months [mean +/- SD],
58 children aged 7.9 +/-3.8 years, 42 adults aged 42.5 +/-5.1 years, and 4
0 elderly subjects aged 71.8 +/-3.4 years, all males). Lesions were quantif
ied by computer-assisted imaging analysis of sections of the middle cerebra
l and basilar arteries, the left anterior descending coronary artery, the c
ommon carotid artery, and the abdominal aorta. Macrophages, apolipoprotein
B, oxidized LDL, and matrix metalloproteinase-9 in lesions were determined
by immunocytochemistry. The effect of aging on atherogenesis was then compa
red with that on the activity of 4 antioxidant enzymes in the arterial wall
.
Results-Atherosclerosis was 6- to 19-fold greater (P <0.01) in extracranial
arteries than in intracranial arteries, and it increased linearly with age
. Intracranial arteries showed significantly greater antioxidant enzyme act
ivities than did extracranial arteries. However, the antioxidant protection
of intracranial arteries decreased significantly in older age, coinciding
with a marked acceleration of atherogenesis. An increase in matrix metallop
roteinase-9 protein expression and in gelatinolytic activity consistent wit
h the degree of intracranial atherosclerosis was also observed.
Conclusions-These results suggest that a greater activity of antioxidant en
zymes in intracranial arteries may contribute to their greater resistance t
o atherogenesis and that with increasing age intracranial arteries respond
with accelerated atherogenesis when their antioxidant protection decreases
relatively more than that of extracranial arteries.