ULTRASTRUCTURAL CHARACTERISTICS OF HUMAN ATHERECTOMY TISSUE FROM CORONARY AND LOWER-EXTREMITY ARTERIAL STENOSES

In animal studies, smooth muscle cell phenotype conversion has been su ggested to be an essential prerequisite for subsequent migratory and p roliferative events leading to (neo)intima formation, To determine ult rastructural characteristics of individual smooth muscle cells and to relate them to specific lesion types and intimal cell density, we comp ared atherectomy samples from 17 restenotic and 32 primary coronary an d peripheral lesions using transmission electron microscopy and histol ogy, Ultrastructural analysis of cell-rich tissue, predominantly of re stenotic origin, revealed smooth muscle cells full of synthetic organe lles, Moreover, these cells were frequently found to be surrounded by loose extracellular matrix and partially fragmented basement membrane components, In contrast, plaques exhibiting low cell density, as exclu sively seen with primary lesions, displayed an extensive buildup of ex tracellular matrix containing sparse numbers of microfilament-rich smo oth muscle cells, The central finding of our study is a morphometrical ly quantitated, twofold greater (p < 0.001) volume fraction of synthet ic organelles (V-s) within smooth muscle cells in restenotic versus pr imary plaques, indicating a more dedifferentiated cellular phenotype a s a typical feature of restenotic lesions, Equally enhanced V-s values were seen for restenotic coronary and peripheral plaques. No V-s decr ease was observed during time after angioplasty (2.2 to 30 months) reg ardless of previous revascularization procedures (balloon or atherecto my), Despite intra- and interlesional variability, V-s and intimal cel l density were strongly correlated (r = 0.74; p < 0.001). This correla tion was observed more often with clinical restenoses and, importantly In a portion (10% to 15%) of primary lesions, Data from restenotic le sions indicate that a dedifferentiated smooth muscle cell phenotype, p ericellular matrix disintegration, and intimal hypercellularity are lo ng-lasting biologic responses to previous smooth muscle cell injury Si milar tissue characteristics expressed in several primary lesions sugg est that comparable pathogenic mechanisms are related to the progressi on and/or acuity of chronic lesions.