Marek J M, Koehler C, Aguirre M L, Westerband A, Gentile A T, Mills J L, Hunter G C
Department of Surgery, Veterans Affairs Medical Center, Tucson, Arizona, USA.
J Surg Res. 1998 Jan;74(1):27-33. doi: 10.1006/jsre.1997.5222.
Although smooth muscle cell proliferation is a prominent feature of restenosis in experimental models, the role of cellular proliferation in the initiation and progression of carotid restenosis is not well documented.
Between 1985 and 1995, 35 carotid endarterectomies (CEA) in 34 patients were performed for restenosis. Patient risk factors, cerebrovascular symptoms, and operative findings were recorded. Tissue specimens from 29 of these cases and 14 original specimens from the same patient were examined by light microscopy (H&E, trichrome, elastochrome, and Alcian blue) and immunohistochemistry (alpha actin, CD 68, vWF, and proliferating nuclear cell antigen (PCNA)) in order to determine the morphologic characteristics and cellular proliferative activity of the plaque.
Hemodynamically significant recurrent stenosis occurred in the 29 patients (69% symptomatic) between 2 months and 30 years after their initial CEAs. Eleven of 29 (38%) lesions were removed early (< 3 years). Recurrent lesions were characterized based on their components as neointimal thickening, 24% (7/29), neointimal thickening and atherosclerosis, 55% (16/29), or atherosclerotic, 21% (6/29). Nineteen of 29 (66%) plaques were complicated by mural thrombus or intraplaque hemorrhage. An inflammatory cell infiltrate consisting of macrophages and T lymphocytes was observed adjacent to areas of recurrent atherosclerosis and macrophages in regions of intimal thickening. Although infrequently present (generally 1-3% of cells) PCNA-positive cells were detected in 41% (12 of 29) of recurrent and 14% (2 of 14) of primary plaques. No PCNA-positive cells were detected in the remaining 67% (29 of 43) of specimens. There was no statistical difference in the number of PCNA-positive cells in early recurrent lesions compared to those recurring after 3 years (36% vs 44%). PCNA immunoreactivity when present was most commonly noted in macrophages associated with thrombus or atheroma rather than smooth muscle cells.
Although evidence of cellular proliferation was observed in 40% of recurrent carotid endarterectomy lesions, the proliferation rate was low (1-3%) and unrelated to the time interval of recurrence. Proliferative activity was most pronounced in macrophages associated with intraplaque hemorrhage or atheroma. The contribution of inflammatory cells to the biologic behavior of restenotic lesions requires further investigation.
尽管在实验模型中平滑肌细胞增殖是再狭窄的一个突出特征，但细胞增殖在颈动脉再狭窄的发生和发展中的作用尚无充分文献记载。
1985年至1995年间，对34例患者进行了35次颈动脉内膜切除术（CEA）以治疗再狭窄。记录患者的危险因素、脑血管症状和手术所见。对其中29例患者的组织标本以及来自同一患者的14份原始标本进行光学显微镜检查（苏木精-伊红染色、三色染色、弹性染色和阿尔辛蓝染色）和免疫组织化学检查（α肌动蛋白、CD 68、血管性血友病因子和增殖细胞核抗原（PCNA）），以确定斑块的形态学特征和细胞增殖活性。
29例患者（69%有症状）在初次CEA术后2个月至30年出现血流动力学上有意义的复发性狭窄。29例病变中有11例（38%）在早期（<3年）被切除。复发性病变根据其成分分为内膜增厚型，占24%（7/29）；内膜增厚和动脉粥样硬化型，占55%（16/29）；或动脉粥样硬化型，占21%（6/29）。29例斑块中有19例（66%）合并壁内血栓形成或斑块内出血。在复发性动脉粥样硬化区域附近观察到由巨噬细胞和T淋巴细胞组成的炎性细胞浸润，在内膜增厚区域观察到巨噬细胞。尽管PCNA阳性细胞很少见（通常占细胞的1 - 3%），但在41%（29例中的12例）复发性斑块和14%（14例中的2例）原发性斑块中检测到PCNA阳性细胞。在其余67%（43例中的29例）标本中未检测到PCNA阳性细胞。早期复发性病变中PCNA阳性细胞数量与3年后复发的病变相比无统计学差异（36%对44%）。当存在PCNA免疫反应性时，最常见于与血栓或动脉粥样瘤相关的巨噬细胞而非平滑肌细胞。
尽管在40%的复发性颈动脉内膜切除病变中观察到细胞增殖的证据，但增殖率较低（1 - 3%）且与复发时间间隔无关。增殖活性在与斑块内出血或动脉粥样瘤相关的巨噬细胞中最为明显。炎性细胞对再狭窄病变生物学行为的贡献需要进一步研究。
