Histopathology of in-stent restenosis in patients with peripheral artery disease
Histopathology of in-stent restenosis in patients with peripheral artery disease
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DOI：
10.1161/01.cir.95.8.1998
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发表时间：
1997-04-15
期刊：
影响因子：
37.8
通讯作者：
Isner, JM
中科院分区：
文献类型：
--
作者：
Kearney, M;Pieczek, A;Isner, JM
背景临床研究表明，平滑肌细胞（SMC）增生是支架内再狭窄的最可能原因。然而，关于这个问题的病理学数据是有限的。具体而言，直接证据的增殖活性在组织切除狭窄stents.Methods和结果组织标本中取出定向粥样斑块切除术从10例支架内再狭窄复杂的外周动脉疾病的经皮血运重建。在细胞特异性免疫染色后定量进行细胞组成分析。对于保存在甲醇中的标本（7/10），通过使用增殖细胞核抗原（PCNA）、细胞周期蛋白E和cdk 2的抗体评价细胞增殖。对8例多聚甲醛保存的标本进行凋亡TUNEL染色。10份标本均含有主要由SMC组成的广泛细胞过多病灶（平均值+/-SEM，59.3+/-3.0%）。在所有7份甲醇保存的标本中均记录了持续增殖活性的证据：24.6+/-2.3%的SMC为PCNA阳性，24.8+/-3.1%为细胞周期蛋白E阳性，22.5+/-2.2%为cdk 2阳性。在所有8份标本中均检测到凋亡细胞，这些标本已适当保存以允许DNA切口末端标记。在10份标本中均鉴定出巨噬细胞和白细胞，但占细胞数量的比例较小（分别为14.5 ± 1.9%和9.5 ± 1.4%）。结论支架内再狭窄是由平滑肌细胞增生引起的，抑制平滑肌细胞增生的治疗方法可进一步提高血管内支架的应用价值。
Background Clinical studies have suggested that smooth muscle cell (SMC) hyperplasia is the most likely cause of in-stent restenosis. However, pathological data regarding this issue are limited. Specifically, direct evidence of proliferative activity in tissues excised from stenotic stents has not been previously reported.Methods and Results Tissue specimens were retrieved by directional atherectomy from 10 patients in whom in-stent restenosis complicated percutaneous revascularization of peripheral artery disease. Analysis of cellular composition was performed quantitatively after cell-specific immunostaining. For specimens preserved in methanol (7 of 10), cellular proliferation was evaluated by use of antibodies to proliferating cell nuclear antigen (PCNA), cyclin E, and cdk2. TUNEL staining for apoptosis was performed on 8 paraformaldehyde-preserved specimens. Each of the 10 specimens contained extensive foci of hypercellularity composed predominantly of SMCs (mean+/-SEM, 59.3+/-3.0%). Evidence of ongoing proliferative activity was documented in all 7 methanol-preserved specimens: 24.6+/-2.3% of SMCs were PCNA-positive, 24.8+/-3.1% were cyclin E-positive, and 22.5+/-2.2% were cdk2-positive. Apoptotic cells were detected in all 8 specimens that had been appropriately preserved to permit DNA nick-end labeling. Macrophages and leukocytes were identified in each of the 10 specimens but accounted for a proportionately smaller number of cells (14.5+/-1.9% and 9.5+/-1.4%, respectively). Organized thrombus was observed in 6 of the 10 specimens.Conclusions These findings support the notion that in-stent restenosis results from SMC hyperplasia and suggest that adjunctive therapies designed to inhibit SMC proliferation may further enhance the utility of endovascular stents.