Exogenous Vascular Endothelial Growth Factor Can Induce Preeclampsia-Like Symptoms in Pregnant Mice

ABSTRACT

It is reported that expression of vascular endothelial growth factor (VEGF) in trophoblasts increases in cases with preeclampsia. Recently, we demonstrated that the lack of cyclin-dependent kinase inhibitor, p57kip2, expression in the fetus and the placenta plays a role in the development of preeclampsia-like symptoms in pregnant mice. Furthermore, we observed that VEGF mRNA and protein levels, especially VEGF₁₆₄, were higher and its expression was stronger in placentas of p57kip2-null embryos than in placentas of wild-type embryos. In this study we investigated whether exogenous murine VEGF₁₆₄ induced preeclampsia-like symptoms in pregnant mice, and anti-VEGF neutralized antibody could suppress these symptoms. Administration of VEGF induced hypercoagulation in the placental circulation and a significant elevation of systolic blood pressure in pregnant mice. Furthermore, we demonstrated that treatment with anti-VEGF antibody could suppress the hypercoagulability in placenta and the elevation of systolic blood pressure. These data suggest that VEGF is related to the pathophysiology of preeclampsia.

KEYWORDS

Vascular endothelial growth factor (VEGF) - hypertension - hypercoagulation - preeclampsia - anti-VEGF antibody

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