Jg. Pickering et al., PROLIFERATIVE ACTIVITY IN PERIPHERAL AND CORONARY ATHEROSCLEROTIC PLAQUE AMONG PATIENTS UNDERGOING PERCUTANEOUS REVASCULARIZATION, The Journal of clinical investigation, 91(4), 1993, pp. 1469-1480
We evaluated the proliferative activity of human atherosclerotic lesio
ns associated with active symptoms of ischemia, by assessing the expre
ssion of the proliferating cell nuclear antigen (PCNA). We confirmed i
n vitro that PCNA, an essential component of the DNA synthesis machine
ry, is selectively expressed in proliferating human vascular smooth mu
scle cells. 37 atherosclerotic lesions (18 primary and 19 restenotic)
retrieved by directional atherectomy from either coronary or periphera
l arteries were then studied for the expression of PCNA, using in situ
hybridization or immunohistochemistry. Among plaques studied by in si
tu hybridization, 7 out of 11 primary and 11 out of 11 restenotic lesi
ons contained PCNA-positive cells. The mean rate of proliferation (per
cent of PCNA-positive cells) was 7.2+/-10.8% in primary lesions and 20
.6+/-18.2% in restenotic lesions (P < 0.05). Among specimens studied b
y immunohistochemistry, five out of seven primary and eight out of eig
ht restenotic lesions contained proliferating cells. The mean rate of
proliferation was again higher in the restenotic (15.2+/-13.6%) than p
rimary (3.6+/-3.5%) lesions (P < 0.05). Proliferating cells were detec
ted as late as 1 yr after angioplasty. We conclude that cellular proli
feration is a feature of atherosclerotic lesions which are associated
with symptoms of ischemia, but that it is more prominent in restenosis
compared to primary lesions. These findings have implications for the
rapies aimed at limiting lesion growth, particularly after percutaneou
s revascularization.