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Am J Hypertens. 2011 May;24(5):606-12. doi: 10.1038/ajh.2010.247. Epub 2010 Dec 23.

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

Author information

1
Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, USA.

Abstract

BACKGROUND:

Pre-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 (AT(1)-AA), that activate the major angiotensin receptor, AT(1). 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 VEGF(121), a relatively stable form of the natural ligand.

METHODS:

Immunoglobulin G (IgG) from women with PE was injected into pregnant mice with or without continuous infusion of recombinant VEGF(121). Injected mice were monitored for symptoms of PE.

RESULTS:

As a result of infusion of recombinant VEGF(121) autoantibody-induced hypertension (systolic blood pressure) was reduced from 159 ± 5 to 124 ± 5 mm Hg, proteinuria from 111 ± 16 to 40 ± 5 mg protein/mg creatinine and blood urea nitrogen levels from 31 ± 1 mg/dl to 18 ± 2 mg/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 AT(1)-AA injection was significantly improved by VEGF(121) infusion.

CONCLUSIONS:

The infusion of recombinant VEGF(121) significantly attenuated autoantibody-induced features of PE.

PMID:
21183928
PMCID:
PMC3262171
DOI:
10.1038/ajh.2010.247
[Indexed for MEDLINE]
Free PMC Article

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