ANALYSIS OF ATHERECTOMY SPECIMENS

Atherectomy specimens may be regarded as biopsy tissue excised from hu man vascular target lesions. Proceeding from contrary histologic findi ngs that attribute focal hypercellularity to restenosis, and hypocellu larity to chronic lesions, further analysis of atherectomy specimens w as performed to study ultrastructural characteristics and functional a spects propagated by both lesion types. Transmission electron microsco py examination showed that intimal smooth muscle cells (SMCs) were the predominant cells in both primary and restenotic lesions. SMCs exhibi ted variable degrees of metabolic activation, typically higher in SMCs of restenotic lesions. This SMC phenotype was equally expressed when tissue samples were placed in a cell culture model. In an attempt to q uantify SMC activity, proliferative as well as migratory activities of cultured cells were measured by growth curves and a computer-assisted motion analysis system, respectively. A 2- to 3-fold increase of both activity determinants was observed with SMCs cultivated from restenot ic lesions compared with those from primary lesions, irrespective of t heir coronary or peripheral origin. Drug-induced interference of human SMC metabolic activation and antagonism to their proliferative and mi gratory activities may be helpful in evaluation of therapeutic concept s to prevent restenosis. The anti-tubulin colchicine was studied for i ts effect on the defined determinants. The data in vitro demonstrate t hat colchicine decreased proliferative and migratory activity of SMCs and caused disorganization of the cytoplasmic ultrastructure. In concl usion, electron microscopy and cell culture studies may help to shed m ore light on the structures and mechanisms underlying restenosis and p laque growth. Deliberate counteractions of any of the specific early e vents implicated in these complex pathobiologic processes may eventual ly become effective means to suppress restenosis and may thus result i n a prophylactic as well as therapeutic treatment of the diseased vasc ular wall.