Fibrous cap thickness and smooth muscle cell apoptosis in high-grade carotid artery stenosis.
OBJECTIVE
There is growing evidence that, in high-grade internal carotid artery (ICA) stenosis, continuous fibrous cap thinning is not mandatory for plaque rupture and symptom development. The possibility that smooth muscle cell (SMC) apoptosis is involved in loss of fibrous cap volume has only been examined in a limited number of patients with high grade carotid artery stenosis.


METHODS
Endarterectomy specimens from n = 38 consecutive patients undergoing surgery for high-grade ICA stenosis (> or = 70%) were transversely sectioned at 2 mm intervals. Plaque instability was defined clinically, by a history of recent ischemic symptoms (< 60 days before surgery; n = 19) attributable to the stenosis, or histopathologically by the presence of plaque rupture (n = 14). Detailed morphometric analyses of the fibrous cap was based on routine stains; for DNA in situ end labeling the TUNEL technique was used. SMCs were identified by immunostaining for SMC actin.


RESULTS
We found no significant difference between symptomatic/asymptomatic or ruptured/unruptured plaque with respect to various morphometric measures of the fibrous cap (i.e. mean area, number of plaque sections with fibrous cap, necrotic core-to-lumen distance at its thinnest or thickest part). The mean (+/- SD) apoptotic SMCs per thousand within the fibrous cap was significantly higher in symptomatic vs. asymptomatic (64.53 +/- 77.3 vs. 6.71 +/- 11.9; P<0.001) but not in ruptured plaques (43.3 +/- 64.4 vs. 30.1 +/- 60.9; P=0.117).


CONCLUSIONS
These data suggest that continuous thinning of the fibrous cap is not an essential prerequisite for plaque rupture in ICA stenosis. Symptomatic, but not ruptured plaque, were associated with the highest number of apoptotic SMC. Thus, it seems unlikely that SMC apoptosis promotes plaque rupture by fibrous cap thinning.
Trostdorf
F
F
Department of Neurology, J.W. Goethe-University Frankfurt am Main, Frankfurt am Main, Germany. f.trostdorf@em.uni-frankfurt.de
Buchkremer
M
M
Harmjanz
A
A
Kablau
M
M
Jander
S
S
Geiger
K
K
Schmitz-Rixen
T
T
Steinmetz
H
H
Sitzer
M
M
D000368:Aged; D017209:Apoptosis; D016893:Carotid Stenosis / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D011446:Prospective Studies