PARENT SESSION
Pregnancy and Parturition

THE INVOLVEMENT OF NITRIC OXIDE IN THE INDUCTION OF PLACENTAL VASCULAR ENDOTHELIAL-CADHERIN BY VASCULAR ENDOTHELIAL GROWTH FACTOR.

Chang, Chih-Ching¹, Chang, Torng-Yow², Tsai, Mei-Ling², ^{1 2}

ABSTRACT- Vascular endothelial (VE)-cadherin, a homotypic adhesion molecule, is involved in capillary formation. VEGF-induced capillary formation requires the presence of VE-cadherin and the production of nitric oxide (NO) in endothelium. VE-cadherin in placenta is a major component of stable adheren junctions. The purpose of this study was to examine whether the induction of VE-cadherin by VEGF was through a NO-dependent pathway. In this study, protein abundance of VE-cadherin was measured by western blot analysis. To characterize the expression profile of VE-cadherin in placenta, pregnant rats on gestation day 14 (G14), 18 (G18) and 21 (G21) were used. The expression of VE-cadherin decreased with the increase of gestation days. To examine the concentration-dependent effect of VEGF on the expression of VE-cadherin, placental explants from G18 rats were cultured in vitro for 24 hr in RPMI containing various doses of VEGF (0.01-100 ng/ml). VEGF elicited dual effects on the expression of VE-cadherin. The low-dose VEGF increased the expression of VE-cadherin, but the high-dose VEGF decreased it. To examine the involvement of NO in the induction of VE-cadherin by VEGF, L-arginine (a substrate for nitric oxide synthase), L-NAME (a competitor for L-arginine), and SNP (a NO donor) were used. L-arginine at 10^-4 M increased the expression of VE-cadherin, but that at 10^-3 M decreased it. In the presence of VEGF, SNP induced the expression of VE-cadherin. L-NAME suppressed the induction of VE-cadherin by VEGF and L-arginine. As our data suggest, the presence of NO may be involved in the induction of VE-cadherin by VEGF.

KEY WORDS: ve-cadherin, VEGF, placenta, nitric oxide