O'Brien E R, Alpers C E, Stewart D K, Ferguson M, Tran N, Gordon D, Benditt E P, Hinohara T, Simpson J B, Schwartz S M
Department of Pathology, University of Washington School of Medicine, Seattle 98195.
Circ Res. 1993 Aug;73(2):223-31. doi: 10.1161/01.res.73.2.223.
On the basis of animal models of arterial injury, smooth muscle cell proliferation has been posited as a dominant event in restenosis. Unfortunately, little is known about this proliferation in the human restenotic lesion. The purpose of this study was to determine the extent and time course of proliferation in primary and restenotic coronary atherectomy-derived tissue. Primary (n = 118) and restenotic (n = 100) coronary atherectomy specimens were obtained from 211 nonconsecutive patients. Immunocytochemistry for the proliferating cell nuclear antigen (PCNA) was used to gauge proliferation in the atherectomy specimens. The identity of PCNA-positive cells was then determined using immunohistochemical cell-specific markers. Eighty-two percent of primary specimens and 74% of restenotic specimens had no evidence of PCNA labeling. The majority of the remaining specimens had only a modest number of PCNA-positive cells per slide (typically < 50 cells per slide). In the restenotic specimens, PCNA labeling was detected over a wide time interval after the initial procedure (eg, 1 to 390 days), with no obvious proliferative peak. Cell-specific immunohistochemical markers identified primary and restenotic PCNA-positive cells as smooth muscle cells, macrophages, and endothelial cells. In conclusion, the findings were as follows: (1) Proliferation in primary and restenotic coronary atherectomy specimens, as indicated by PCNA labeling, occurs infrequently and at low levels. (2) The response to injury in existing animal models of angioplasty may follow a very different course of events from the clinical reality in human atherosclerotic coronary arteries and may help explain why current approaches to restenosis therapy have been ineffective.
基于动脉损伤的动物模型，平滑肌细胞增殖被认为是再狭窄中的主要事件。遗憾的是，对于人类再狭窄病变中的这种增殖情况了解甚少。本研究的目的是确定原发性和再狭窄性冠状动脉旋切术获取组织中增殖的程度和时间进程。从211例非连续患者中获取原发性（n = 118）和再狭窄性（n = 100）冠状动脉旋切术标本。使用增殖细胞核抗原（PCNA）免疫细胞化学方法来评估旋切术标本中的增殖情况。然后使用免疫组织化学细胞特异性标记物确定PCNA阳性细胞的类型。82%的原发性标本和74%的再狭窄性标本没有PCNA标记的证据。其余大多数标本每张载玻片上只有少量PCNA阳性细胞（通常每张载玻片<50个细胞）。在再狭窄性标本中，在初次手术后很长一段时间内（例如1至390天）都能检测到PCNA标记，没有明显的增殖高峰。细胞特异性免疫组织化学标记物将原发性和再狭窄性PCNA阳性细胞鉴定为平滑肌细胞、巨噬细胞和内皮细胞。总之，研究结果如下：（1）如PCNA标记所示，原发性和再狭窄性冠状动脉旋切术标本中的增殖很少发生且水平较低。（2）现有血管成形术动物模型中对损伤的反应可能与人类动脉粥样硬化性冠状动脉的临床实际情况有很大不同，这可能有助于解释为什么目前的再狭窄治疗方法无效。
