INTIMAL CELL-DENSITY IN POSTANGIOPLASTY VERSUS PRIMARY CORONARY AND PERIPHERAL LESIONS - A SYSTEMATIC STUDY ON HUMAN ATHERECTOMY SAMPLES

Our knowledge of the identity and functional significance of the patho genic mechanisms responsible for restenosis and arteriosclerosis in nm n is still limited. Among others, phenotypic conversion, migration, an d proliferation of smooth muscle cells have been suggested to lead to hypercellular neointima. In the present study, we examined intimal cel l numbers and cell types lit tissue of 23 postangioplasty lesions biop sied by directional atherectomy, using histology and transmission elec tron microscopy. Comparative tissue analysis was performed for 53 prim ary lesions, Tissue specimens obtained from coronary (n = 32) and peri pheral lesions (n = 44) of 69 symptomatic patients were analyzed. Hist ological assessment of cell density showed intra and interlesional var iability. A markedly (P < 0.001) higher cellularity was found in posta ngioplasty compared to primary lesions, irrespective of coronary or pe ripheral origin. Cell density in renarrowed tissue following angioplas ty (2 to 30 months) did not significantly decrease regardless of previ ous balloon dilatation or atherectomy. Wizen categorizing intimal cell density, postangioplasty lesion hypercellularity (75th percentile; > 514 cells/mm(2)) was observed in 12/23 lesions (52%), but hypocellular ity (25th percentile; < 76 cells/mm(2)) in none. hi contrast, primary lesions were more variable, with hypercellularity in 7/53 plaques (13% ), and hypocellularity in 19/53 (36%), Transmission electron microscop ic analysis of subcellular features revealed hypocellular plaques to h ave ail extensive build-up of extracellular matrix, with only sparsely embedded smooth muscle cells (SMCs). These SMCs have a range of inter mediate to microfilament-rich contractile phenotypes, thereby indicati ng only marginal metabolic activity. In contrast, hypercellular plaque regions contained predominantly organelle-filled SMCs, irrespective o f postangioplasty or primary origin. In conclusion, increased SMC dens ity was observed predominantly in most renarrowed lesions encompassing classical restenoses (2 to 6 months post angioplasty) as well as late recurrent lesions (7 to 30 months postangioplasty). Concordantly, pri mary lesion hypercellularity is suggested to be related to the formati on and progression of native arteriosclerosis.