Relation between Activated Smooth-Muscle Cells in Coronary-Artery Lesions and Restenosis after Atherectomy

Abstract

Background: Neointimal proliferation leading to restenosis frequently develops after coronary angioplasty. This process is associated with a change in vascular smooth-muscle cells from a contractile (quiescent) phenotype to a synthetic or proliferating (activated) one. We investigated whether the presence of activated smooth-muscle cells in coronary lesions at the time of coronary atherectomy predisposes patients to subsequent restenosis. Methods: We used in situ hybridization to study the expression of messenger RNA in coronary-atherectomy specimens from 20 patients. Plaque material was hybridized with a probe for the B isoform of human nonmuscle myosin heavy chain, a major nonmuscle myosin isoform in activated, but not quiescent, smooth-muscle cells. Angiographic follow-up data were obtained a mean (±SD) of 174 ±54 days after atherectomy in 16 of the 20 patients, and the extent of recurrent luminal narrowing was analyzed quantitatively. The presence of restenosis was assessed by exercise thallium scintigraphy in the other four patients. Results: Atherectomy specimens from 10 of the 20 patients showed hybridization with the probe, defined as the clustering of more than 20 silver grains per cell nucleus in more than 10 nuclei in five high-power fields (x250); specimens from the other 10 patients showed no such hybridization. At follow-up, restenosis had developed in 8 of the 10 patients with positive hybridization results, but was absent in 9 of the 10 patients with negative results (P = 0.007). The degree of late loss in luminal diameter was significantly higher in patients with positive hybridization results than in those with negative results (ratio of late loss to immediate gain after atherectomy, 0.76 ±0.3 vs. 0.36 ±0.3; P<0.001). Conclusions: We conclude that the expression of the B isoform of nonmuscle myosin heavy chain is increased in some coronary atherosclerotic plaques and that this increase in expression identifies a group of lesions at high risk for restenosis after atherectomy., Restenosis after coronary angioplasty is a major clinical problem. Within six months, clinically important stenosis recurs at the site of angioplasty in 35 to 45 percent of patients who have undergone a single-vessel procedure, and in 50 to 60 percent of those who have undergone multivessel angioplasty1. Although a variety of clinical, anatomical, and technical factors2 have been associated with the subsequent development of restenosis, accurate predictions for individual patients and lesions are not possible. A number of studies have demonstrated that the hallmark of restenosis is the abundant proliferation of neointimal smooth-muscle cells3,4. Similar pathological findings… © 1993, Massachusetts Medical Society. All rights reserved.