23: Effect of continuous delivery of recombinant vascular endothelial growth factor on vascular reactivity in a SFLT-1 induced animal model of preeclampsia


      Maternal vascular dysfunction has been implicated in the pathogenesis of preeclampsia and confirmed in an animal model of preeclampsia induced by over-expression sFlt-1. Our objective was to evaluate the effect of exogenous vascular endothelial growth factor (VEGF) on in-vitro vascular function in the sFlt-1 mouse model of preeclampsia.

      Study Design

      At day 8 of gestation, CD-1 pregnant mice were randomly allocated to continuous 0.5 μl/hr osmotic infusion of either VEGF-121 (400 μg/kg/day) or phosphate buffered-saline (solvent control) for 10 days. At day 9, animals were injected with adenovirus carrying sFlt-1 (109 PFU). At day 18 of gestation, the mice were sacrificed and 2 mm segments of carotid artery were mounted in a wire myograph for isometric tension recording. Contractile responses to KCl (10−5 M) and concentration-response curves (10−10-10−5 M) to acetylcholine (Ach, endothelium dependent vasodilator), sodium nitroprusside (SNP, endothelium independent vasodilator), phenylephrine (PE), and thromboxane A2 (TxA2, 10−10-10−6 M) were obtained. ANOVA, Newman-Keuls, and Student t tests were used for statistical analysis (significance: p<0.05).


      Responses to KCl were not significantly different between the groups. The maximal effect (ME) of PE did not differ between the VEGF and control groups (90.92 ± 7.39 and 91.69 ± 8.48 mN; p=0.95). The contractile response was also similar in the presence of the nitric oxide synthase inhibitor L-NAME. Conversely, ME to TxA2 was significantly higher in the control versus VEGF group (200.27 ± 27.17 vs 175.97 ± 14.90 mN, p=0.03). Response to SNP was significantly higher in the VEGF group compared with the control group (102.26 ± 1.38 and 84.01 ± 12.76 mN, p=0.03). Response to Ach did not differ between the two groups.


      VEGF-121 therapy led to improvement of vascular function, but did not reverse completely the vascular abnormalities seen in this animal model of preeclampsia. Neovascularization, sFlt-1 inhibition, new vasodilator pathway may be implicated in the improved vascular function.