title: 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 VEGF (164), 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 VEGF (164) 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.
authors.affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murakami
authors.forename: Takao
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Kohei
authors.initials: K
authors.lastname: Omatsu
authors.forename: Mika
authors.initials: M
authors.lastname: Suzuki
authors.forename: Ryota
authors.initials: R
authors.lastname: Ohashi
authors.forename: Toshiki
authors.initials: T
authors.lastname: Matsuura
authors.forename: Motoi
authors.initials: M
authors.lastname: Sugimura
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kanayama
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D000990:Antithrombin III / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D051379:Mice; D010447:Peptide Hydrolases / Q000097:blood; D010920:Placenta / Q000737:chemistry; D011225:Pre-Eclampsia / Q000139:chemically induced* / Q000188:drug therapy / Q000209:etiology; D011247:Pregnancy; D019851:Thrombophilia / Q000139:chemically induced / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D042461:Vascular Endothelial Growth Factor A; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases