Increased immunohistochemical expression of thrombomodulin at placental perivascular myofibroblast in severe preeclampsia (PE).
The presence of pro-coagulant and anti-coagulant components of the placental vascular endothelium and syncytiotrophoblast are essential for homeostasis. Vascular endothelium prevents blood clot formation in vivo by involving a cell surface thrombin-binding glycoprotein, thrombomodulin (TM), that activates plasma anti-coagulant protein C. The TM levels increase during pregnancy, but the fibrinolytic capacity diminishes. Since vascular lesions with placental coagulation disorders can be associated with preeclampsia (PE), we hypothesized that TM expression in the stem villous vasculature and syncytiotrophoblast of the placenta are impaired in PE. Plasma and placental tissue samples were collected from PE (n=12) and normotensive pregnant patients (n=11). Patient's gestational age was 35.7+/-1.2 (normotensive) and 30.6+/-1.5 weeks (PE). Blood samples were drawn 30 min before delivery. Serum PAI-1 and PAI-2 antigens were determined by enzyme-linked immunoabsorbent assay (ELISA). A monoclonal antibody specific for TM was used for immunohistochemical tissue staining (ABC) and the staining was quantified by semi quantitative scores. Results show no intensity differences at the apical syncytiotrophoblast between the two groups. However, in preeclamptic placenta, TM expression diminished in the endothelium of the stem villi arteries and increased in the perivascular and stromal myofibroblats in cases of severe PE. TM changes were associated with an increased PAI-1/PAI-2 ratio. It is suggested that in severe PE, the decreased placental blood flow may be due to structural and functional impairment of the endothelium of the stem villi vessels and the surrounding perivascular and stromal myofibroblast, by increasing TM expression which may modulate fetal blow flow in the villous tree.
Bosco
C
C
Anatomy and Development Biology Program, Molecular and Clinical Pharmacology Program and Pathology Program, ICBM Faculty of Medicine, University of Chile, Santiago. cbosco@med.uchile.cl
Parra
M
M
Barja
P
P
Rodrigo
R
R
Fernández
V
V
Suarez
M
M
Muñoz
H
H
D000199:Actins / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017396:Plasminogen Activator Inhibitor 2 / Q000097:blood; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D012720:Severity of Illness Index; D018180:Thrombomodulin / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology
D000199:Actins; D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D011257:Pregnancy Proteins; C051321:SERPINE1 protein, human; D018180:Thrombomodulin; D005337:Fibrin