Simons M, Leclerc G, Safian R D, Isner J M, Weir L, Baim D S
Charles A. Dana Research Institute, Boston, MA.
N Engl J Med. 1993 Mar 4;328(9):608-13. doi: 10.1056/NEJM199303043280903.
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.
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.
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).
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.
冠状动脉血管成形术后常发生导致再狭窄的新生内膜增生。这一过程与血管平滑肌细胞从收缩（静止）表型转变为合成或增殖（激活）表型有关。我们研究了冠状动脉旋切术时冠状动脉病变中激活的平滑肌细胞的存在是否会使患者易发生随后的再狭窄。
我们使用原位杂交技术研究了20例患者冠状动脉旋切术标本中信使核糖核酸的表达。斑块材料与针对人非肌肉肌球蛋白重链B亚型的探针杂交，该亚型是激活而非静止的平滑肌细胞中的一种主要非肌肉肌球蛋白亚型。在20例患者中的16例旋切术后平均（±标准差）174±54天获得血管造影随访数据，并对复发性管腔狭窄程度进行定量分析。另外4例患者通过运动铊闪烁显像评估再狭窄的存在情况。
20例患者中有10例的旋切术标本显示与探针杂交，定义为在五个高倍视野（×250）中每个细胞核有超过20个银颗粒聚集在超过10个细胞核中；另外10例患者的标本未显示这种杂交。随访时，杂交结果为阳性的10例患者中有8例发生了再狭窄，而杂交结果为阴性的10例患者中有9例未发生再狭窄（P = 0.007）。杂交结果为阳性的患者管腔直径的晚期丢失程度显著高于杂交结果为阴性的患者（旋切术后晚期丢失与即刻获得的比值，0.76±0.3对0.36±0.3；P < 0.001）。
我们得出结论，非肌肉肌球蛋白重链B亚型在一些冠状动脉粥样硬化斑块中的表达增加，并且这种表达增加确定了一组旋切术后再狭窄风险高 的病变。
