Apoptosis in restenosis versus stable-angina atherosclerosis: implications for the pathogenesis of restenosis.
Decreases in programmed cell death (apoptosis) may contribute to restenotic hyperplasia by prolonging the life span of intimal cells. Apoptotic events were compared in restenotic versus primary lesions, by using atherectomy samples from 16 restenotic and 30 primary human peripheral and coronary lesions from patients presenting with stable angina. We used transmission electron microscopy to identify apoptosis, quantify its frequency, distinguish apoptosis from necrosis, and relate these events to cellular composition. Smooth muscle cell (SMC) density was higher in restenotic versus primary lesions (P<0.0001), whereas the number of macrophages was significantly reduced (P<0.01) and the number of lymphocytes was lower, but not significantly (P=0.06). As the main finding, restenotic lesions contained fewer apoptotic cells compared with primary lesions (3% versus 13%, P=0.002), whereas no differences were found for cellular necrosis. With regard to cell type, the lower frequency of apoptotic cells observed in restenotic tissue was attributable to both SMCs and macrophages. The key finding of less apoptosis in restenotic versus primary lesions was in agreement with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis (2% versus 9%, P<0.001). For all lesions analyzed, significant inverse correlations were observed between the density of SMCs and the frequency of apoptotic cell death (r=-0.60, P<0.001) as well as the density of SMCs and that of macrophages (r=-0.74, P<0.001). No relationship was seen between the frequency of apoptosis and the density of macrophages. In conclusion, the data of the present study indicate that a low level of apoptosis may be an important mechanism leading to restenotic intimal lesion development after interventional procedures.
Bauriedel
G
G
Department of Internal Medicine/Cardiology, University of Bonn, Germany.
Schluckebier
S
S
Hutter
R
R
Welsch
U
U
Kandolf
R
R
Lüderitz
B
B
Prescott
M F
MF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000473:pathology*; D017209:Apoptosis; D001161:Arteriosclerosis / Q000473:pathology*; D017073:Atherectomy; D002452:Cell Count; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D005263:Femoral Artery / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007083:Iliac Artery / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology*