[Incidence and localization of apoptosis bodies in human arteriosclerosis lesions]

Increased density of smooth muscle cells is an accepted feature of human restenosis after angioplasty. In addition to migration and proliferation, deregulated forms of programmed cell death may represent pathogenic mechanisms which lead to increased intimal cellularity. The goal of the present study was (i) to demonstrate programmed cell death in human plaque tissue by the detection of apoptotic bodies and to distinguish it from cellular necrosis, (ii) to evaluate the frequency and the localization of apoptotic bodies, and (iii) to compare restenotic and primary lesions for different expression patterns. To this end, coronary and peripheral atherectomy specimens from 14 restenotic and 25 primary lesions were examined by electron microscopy and morphometric analysis. Apoptotic bodies were distinguished from cellular necroses due to distinct morphological features, and were observed extracellularly, isolated or cell membrane-bound, as well as intracellularly in smooth muscle cells and macrophages. The main finding of this study is that hypercellular restenotic tissue from both coronary and peripheral lesions contains fewer apoptotic bodies than hypocellular plaques from primary lesions (p < 0.01 and p < 0.05, respectively). Most importantly, a highly significant, inverse correlation was seen between the density of apoptotic bodies and intimal cellularity (r = -0.67; p < 0.0001). Especially in the extracellular matrix regions, restenotic lesions showed fewer apoptotic bodies (p < 0.001). Again, these plaques exhibited a smaller number of apoptotic bodies with intracellular or membrane-bound localization; however, this observation was without statistical significance compared to primary lesions. For both plaque types, apoptotic bodies were found more frequently (by the factor 4-10) in the presence of smooth muscle cells than with macrophages. With respect to the cellular composition of the plaques, apoptotic bodies were evenly detected in 15-28% of all smooth muscle cells and macrophages. Our results document a considerable intimal density of apoptotic bodies in high-grade human arteriosclerotic lesions and, in addition, reveal nearby smooth muscle cells and macrophages exhibiting intensive phagocytotic capacity. Differences in the density of apoptotic bodies and in cellularity, coincident with an inverse correlation between these determinants, were observed for restenotic and primary tissue. These findings strongly point to deregulated forms of programmed cell death as important pathogenic mechanisms involved in human restenosis.