Expression of angiopoietins 1, 2 and their common receptor tie-2 in relation to the size of endothelial lining gaps and expression of VEGF and VEGF receptors in idiopathic menorrhagia.
OBJECTIVE
To investigate whether idiopathic menorrhagia (IM) is associated with alterations of the vascular expression of angiopoietin-1, angiopoietin-2, and tie-2 receptor.


METHODS
Prospective clinical study.


METHODS
University Hospital, Department of Gynecology.


METHODS
Twenty-four patients with IM and 18 women with eumenorrhea.


METHODS
Endometrial samples underwent immunohistochemical staining for CD34, angiopoetin-1, angiopoietin-2, tie-2, and smooth muscle actin-alpha. Previously published data on gap size and expression of vascular endothelial growth factor family members were used.


METHODS
Differences in immunostaining for these markers by computer-assisted stereological analysis.


RESULTS
There was significantly more angiopoetin-1 positive vessels in IM in the secretory phase, but not of angiopoetin-2 and tie-2, compared with controls. Densities of angiopoetin-1 positive vessels correlated significantly to those of angiopoetin-2 and vascular endothelial growth factor receptor 3. Smooth muscle actin-alpha positive pericytes covered the gaps. Double staining for CD34 and tie-2 receptor was partly identical, but gaps were covered by tie-2 stain.


CONCLUSIONS
The discrete deregulation observed of the angiopoetin-1 expression before menstruation might affect vascular integrity, thereby contributing to the excessive blood loss in IM.
Mints
Miriam
M
Department of Clinical Science, Division of Obstetrics and Gynaecology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. miriam.mints@telia.com
Blomgren
Bo
B
Palmblad
Jan
J
D000328:Adult; D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D004717:Endometrium / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008595:Menorrhagia / Q000378:metabolism* / Q000473:pathology; D008598:Menstruation / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism; D011446:Prospective Studies; D042787:Receptor, TIE-2 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3