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Objective To determine whether vascular endothelial growth factor (VEGF) concentrations are altered in Design Serum was prepared from peripheral venous blood and stored at -70°C. Serum VEGF Setting University of Glasgow Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. Participants Twenty-two healthy nonpregnant volunteer women, 34 normal pregnant women and 34 women with pre-eclampsia were studied.Results Serum concentrations of VEGF were significantly lower in normal pregnant women (median value 12.89 pg/mL) than in nonpregnant women (median value 166 pg/mL; P < 0-0001). In preeclampsia VEGF concentrations were significantly lower (median value 2.34 pg/mL) than normal pregnancies (P < 0.0001). Postpartum concentrations of VEGF in the group complicated by preeclampsia (median value 76.42 pg/mL) were not significantly different fiom nonpregnant values ( P = 0.2).Conclusions Our results show that serum concentrations of VEGF are suppressed in pregnancy and further reduced in pre-eclampsia. Further studies to elucidate the mechanisms which lead to a reduction in VEGF concentrations may provide new clues to the aetiology of this disorder.pre-eclampsia.concentrations were measured by ELISA. INTRODUCTIONPre-eclampsia complicates up to 15% of pregnancies and remains the major cause of maternal death in the United Kingdom today'. It is also a major contributor to maternal morbidity and fetal morbidity and mortality. The aetiology of pre-eclampsia remains unclear, and the only established cure for the disease is delivery of the fetus and placenta. Pre-eclampsia is associated with endothelial damage and dysfunction*. There is a deficiency of antithrombotic and vasodilator factors such as prostacyclin3, increased concentrations of vasoconstrictor products such as endothelin4 and an excess of prothrombotic products such as von Willebrand factolj and cell adhesion molecules VCAM-16 and ESelectin7. Further evidence of endothelial damage in this condition include elevated fibronectin concentrations8, increased capillary permeability9, elevated concentrations of thrombomodulin1° and characteristic lesions such as those seen in glomerular capillary endothelial cells". The endothelial damage is also associated with neutrophil activation12 and platelet activation13 which will promote further vascular damage through a positive feedback loop.The trigger which initiates endothelial damage in pre-eclampsia is unclear; however there is considerable evidence linking it with impaired trophoblast invasion of maternal placental bed spiral arteries14. It has been postulated that the latter defect may result in not only poor fetoplacental perfusion, but also the release of a factor, or factors, into the maternal circulation leading to widespread maternal endothelial damage and the clinical symptoms of the dis~rder'~.Vascular endothelial growth factor (VEGF) is a homodimeric glycosylated heparin-binding glycoprotein16J7 first identified in pituitary folliculo-stellate cells18. It is selectively mitogenic for endothelial ce...

Objective To determine whether circulating levels of cell adhesion molecules, markers of endothelial damage and leucocyte activation, were increased in pre‐eclampsia. Design Serum was prepared from peripheral venous blood and stored at –70°C. The cell adhesion molecules, VCAM‐1, E‐Selectin and ICAM‐1, were measured by ELISA. Setting Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. Subjects Sixteen primigravid women with pre‐eclampsia were recruited for the study. The pre‐eclampsia group were compared with 18 healthy primigravid women with uncomplicated pregnancies. Results The pre‐eclamptic group had significantly higher serum levels of the cell adhesion molecule VCAM‐1 (t= 3.673; P < 0.001). There were no significant differences in the adhesion molecules ICAM‐1 or E‐Selectin. Conclusions Endothelial damage and dysfunction are common to all the pathological features of pre‐eclampsia. This study shows that concentrations of cell adhesion molecules, which indicate leucocyte‐endothelial attachment and activation, are elevated in the serum of patients with pre‐eclampsia. Such increases in soluble circulating cell adhesion molecules may reflect increased expression of these molecules on the endothelium and thereby explain the mechanism for leucocyte activation in pre‐eclampsia.

Endothelial injury is common to all pathological features of preeclampsia. Neutrophil activation has been implicated in the pathophysiology of preeclampsia and requires binding and transmigration of neutrophils through the endothelium. This occurs via an interaction of endothelial adhesion molecules and surface receptors on neutrophils. Upon activation, neutrophil granules are released, the contents of which are capable of mediating vascular damage. In addition, leukotrienes are synthesized, and superoxide is generated in a respiratory burst. These products also provoke vascular damage. Neutrophil recruitment to the endothelium involves express of P-selectin and released of platelet activating factor from the endothelium. In preeclampsia there is evidence of an increase in neutrophil activation with up-regulation of neutrophil integrin expression and increased regulation of the protease elastase. Furthermore, these markers of neutrophil activation correlate with established markers of disease severity. The primary mechanism of neutrophil activation is unknown, but neutrophils in preeclampsia appear to have normal motor activity. Several potential mechanisms of neutrophil activation have been identified. They include up-regulation of cellular adhesion molecules on the endothelial surface, increased generation of tumor necrosis factor-alpha, and endothelial activation from hyperlipidemia. In additional to activation of neutrophils in preeclampsia, there may be involvement of the interleukin-6 and endothelin-1 in "priming" neutrophils for subsequent superoxide production. Activated neutrophils are likely to play a large part in the arteriopathy and endothelial damage associated with preeclampsia, but it is unclear whether neutrophil activation is the cause or the consequence of endothelial damage.

The purpose of this study was to localize intercellular adhesion molecule (ICAM)-1 and ICAM-2 in human endometrium and myometrium throughout the menstrual cycle, and to determine whether the expression of these molecules is regulated by interferon (IFN)-gamma. ICAM-1 and ICAM-2 distribution was examined in endometrial biopsies by immunocytochemistry, and Northern blotting was used to quantify ICAM-1 and ICAM-2 mRNA expression in isolated endometrial glands. Stromal fibroblast cultures were exposed to IFN-gamma and the effect on expression of ICAM-1 and ICAM-2 was determined by immunocytochemistry and Northern blotting. ICAM-1 was localized in vivo to the apical surface of the glandular epithelium, the vascular endothelium and endometrial stromal cells throughout the menstrual cycle. Stromal expression of ICAM-1 was up-regulated in menstrual specimens. Northern blotting confirmed the presence of ICAM-1 mRNA in isolated endometrial glands. The expression of ICAM-1 antigen and message was increased in stromal cell culture after incubation with IFN-gamma in a time-dependent manner, suggesting that this cytokine stimulates the expression of ICAM-1 in the endometrial stroma. ICAM-2 antigen expression was restricted to the vascular endothelium. ICAM-2 mRNA was absent in endometrial glands. The widespread distribution of ICAM-1 in human endometrium suggests that this molecule is involved in the process of menstruation, the functioning of glands, blood vessels and stroma, and in regulating leukocyte trafficking into the tissue. ICAM-2 is restricted to the vascular endothelium where it might modulate leukocyte invasion of the stroma and myometrial connective tissue.