Van Langendonckt A, Punyadeera C, Kamps R, Dunselman G, Klein-Hitpass L, Schurgers L J, Squifflet J, Donnez J, Groothuis P
Department of Gynecology, Université Catholique de Louvain, 1200 Brussels, Belgium.
Mol Hum Reprod. 2007 Dec;13(12):875-86. doi: 10.1093/molehr/gam073. Epub 2007 Nov 6.
To identify specific markers of rectovaginal endometriotic nodule vasculature, highly enriched preparations of vascular endothelial cells and pericytes were obtained from endometriotic nodules and control endometrial and myometrial tissue by laser capture microdissection (LCM), and gene expression profiles were screened by microarray analysis. Of the 18 400 transcripts on the arrays, 734 were significantly overexpressed in vessels from fibromuscular tissue and 923 in vessels from stromal tissue of endometriotic nodules, compared with vessels dissected from control tissues. The most frequently expressed transcripts included known endothelial cell-associated genes, as well as transcripts with little or no previous association with vascular cells. The higher expression in blood vessels was further corroborated by immunohistochemical staining of six potential markers, five of which showed strong expression in pericytes. The most promising marker was matrix Gla protein, which was found to be present in both glandular epithelial cells and vascular endothelial cells of endometriotic lesions, although it was barely expressed at all in normal endometrium. LCM, combined with microarray analysis, constitutes a powerful tool for mapping the transcriptome of vascular cells. After immunohistochemical validation, markers of vascular endothelial and perivascular cells from endometriotic nodules could be identified, which may provide targets to improve early diagnosis or to selectively deliver therapeutic agents.
为了识别直肠阴道内异症结节脉管系统的特异性标志物，通过激光捕获显微切割（LCM）从内异症结节以及对照子宫内膜和子宫肌层组织中获取高度富集的血管内皮细胞和平滑肌周细胞制剂，并通过微阵列分析筛选基因表达谱。与从对照组织中切割的血管相比，阵列上的18400个转录本中，有734个在纤维肌组织的血管中显著过表达，923个在内异症结节间质组织的血管中显著过表达。最常表达的转录本包括已知的内皮细胞相关基因，以及以前与血管细胞关联很少或没有关联的转录本。通过对六个潜在标志物的免疫组织化学染色进一步证实了在血管中的较高表达，其中五个在平滑肌周细胞中显示强表达。最有前景的标志物是基质Gla蛋白，发现其存在于内异症病变的腺上皮细胞和血管内皮细胞中，而在正常子宫内膜中几乎不表达。LCM与微阵列分析相结合，构成了绘制血管细胞转录组的强大工具。经过免疫组织化学验证后，可以识别内异症结节的血管内皮细胞和血管周细胞标志物，这可能为改善早期诊断或选择性递送治疗药物提供靶点。
