APOPTOSIS IN RESTENOSIS VERSUS STABLE-ANGINA ATHEROSCLEROSIS - IMPLICATIONS FOR THE PATHOGENESIS OF RESTENOSIS

Decreases in programmed cell death (apoptosis) may contribute to reste notic hyperplasia by prolonging the rife span of intimal cells. Apopto tic events were compared in restenotic versus primary lesions, by usin g atherectomy samples from 16 restenotic and 30 primary human peripher al and coronary lesions from patients presenting with stable angina. W e used transmission electron microscopy to identify apoptosis, quantif y 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 nu mber 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 w ith primary lesions (3% versus 13%, P=0.002), whereas no differences w ere found for cellular necrosis. With regard to cell type, the lower f requency of apoptotic cells observed in restenotic tissue was attribut able to both SMCs and macrophages. The key finding of less apoptosis i n restenotic versus primary lesions was in agreement with terminal deo xynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) anal ysis (2% versus 9%, P<0.001), For all lesions analyzed, significant in verse correlations were observed between the density of SMCs and the f requency of apoptotic cell death (r= -0.60, P<0.001) as well as the de nsity of SMCs and that of macrophages (r= -0.74, P<0.001). No relation ship was seen between the frequency of apoptosis and the density of ma crophages. In conclusion, the data of the present study indicate that a low level of apoptosis may be an important mechanism leading to rest enotic intimal lesion development after interventional procedures.