Recombinant vascular endothelial growth factor 121 attenuates autoantibody-induced features of pre-eclampsia in pregnant mice

Abstract

BackgroundPre-eclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by excessive production of a soluble form of the vascular endothelial growth factor (VEGF) receptor-1, termed soluble fms-like tyrosine kinase-1 (sFlt-1). This placental-derived factor is believed to be a key contributor to the clinical features of PE. Women with PE are also characterized by the presence of autoantibodies, termed angiotensin type 1 receptor activating autoantibody (AT1-AA), that activate the major angiotensin receptor, AT1. These autoantibodies cause clinical features of PE and elevated sFlt-1 when injected into pregnant mice. The research reported here used this autoantibody-injection model of PE to assess the therapeutic potential of recombinant VEGF121, a relatively stable form of the natural ligand.MethodsImmunoglobulin G (IgG) from women with PE was injected into pregnant mice with or without continuous infusion of recombinant VEGF121. Injected mice were monitored for symptoms of PE.ResultsAs a result of infusion of recombinant VEGF121 autoantibody-induced hypertension (systolic blood pressure) was reduced from 159 5 to 124±5mmHg, proteinuria from 111±16 to 40±5mg protein/mg creatinine and blood urea nitrogen levels from 31±1mg/dl to 18±2mg/dl, P 0.05. Histological analysis revealed that autoantibody-induced glomerular damage including the narrowing of Bowman's space and occlusion of capillary loop spaces was largely prevented by VEGF 121 infusion. Finally, impaired placental angiogenesis resulting from AT1-AA injection was significantly improved by VEGF121 infusion.ConclusionsThe infusion of recombinant VEGF 121 significantly attenuated autoantibody-induced features of PE. © 2011 American Journal of Hypertension, Ltd.