Intimal Cell Density in Postangioplasty Versus Primary Coronary and Peripheral Lesions: A Systematic Study on Human Atherectomy Samples

Abstract

Our knowledge of the identity and functional significance of the pathogenic mechanisms responsible for restenosis and arteriosclerosis in man is still limited. Among others, phenotypic conversion, migration, and proliferation of smooth muscle cells have been suggested to lead to hypercellular neointima. In the present study, we examined intimal cell numbers and cell types in tissue of 23 postangioplasty lesions biopsied by directional atherectomy. using histology and transmission electron microscopy. Comparative tissue analysis was performed for 53 primary lesions. Tissue specimens obtained from coronary (n = 32) and peripheral lesions (n = 44) of 69 symptomatic patients were analyzed. Histological assessment of cell density showed intra‐ and interlesional variability. A markedly (P < 0.001) higher cellularity was found in postangioplasty compared to primary lesions, irrespective of coronary or peripheral origin. Cell density in renarrowed tissue following angioplasty (2 to 30 months) did not significantly decrease regardless of previous balloon dilatation or atherectomy. When categorizing intimal cell density, postangioplasty lesion hypercellularity (75th percentile; > 514 cells/mm2) was observed in 12/23 lesions (52%), but hypocellularity (25th percentile; < 76 cells/mm2) in none. In contrast, primary lesions were more variable, with hypercellularity in 7/53 plaques (13%), and hypocellularity in 19/53 (36%). Transmission electron microscopic analysis of subcellular features revealed hypocellular plaques to have an extensive build‐up of extracellular matrix, with only sparsely embedded smooth muscle cells (SMCs). These SMCs have a range of intermediate to microfilament‐rich contractile phenotypes, thereby indicating only marginal metabolic activity. In contrast, hypercellular plaque regions contained predominantly organelle‐filled SMCs, irrespective of postangioplasty or primary origin. In conclusion, increased SMC density 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, primary lesion hypercellularity is suggested to be related to the formation and progression of native arteriosclerosis.