Mol. Hum. Reprod. Advance Access published online on November 6, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gam073
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Identification of novel antigens in blood vessels in rectovaginal endometriosis
a Department of Gynecology, Université Catholique de Louvain, 1200 Brussels, Belgium b Department of Obstetrics and Gynecology, Research Institute for Growth and Development, 6202 AZ Maastricht, the Netherlands c Cardiovascular Research Institute and VitaK BV, Maastricht University and University Hospital, 6202 AZ Maastricht, the Netherlands d Department of Molecular Diagnostics, Philips Research Europe, High Tech Campus 11, 5656AE, Eindhoven, the Netherlands
* To whom correspondence should be addressed
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 to 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 6 potential markers, 5 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, while it was barely expressed at all in normal endometrium.
Laser capture microdissection, 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.
Key Words: angiogenesis/rectovaginal endometriosis/laser capture microdissection/microarray/vascular targeting
Submitted on June 12, 2007; accepted on September 21, 2007.
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