P35. Novel interaction of placental caveolin-1 expression with markers of oxidative stress and the renin-angiotensin system (RAS) in pre-eclampsia

Abstract

Introduction Caveolin-1 (cav-1) is one of the major protein components of caveolae required for the coordination of some signalling pathways, including that of angiotensin II (AngII) with its Type 1 receptor (AT1R). We have previously reported decreased cav-1 and increased AT1R protein expression in placentae from women with pre-eclampsia (PE). Within the PE placenta, an increase in AngII acting via AT1R may lead to increased vasoconstriction, but possible functional effects of altered cav-1, and interactions with components of RAS and markers of oxidative stress have not been investigated. Objective To establish mechanistic interactions of placental cav-1 with RAS components and surrogate markers of oxidative stress and antioxidant concentrations. Methods Immunohistochemistry was performed on paraffin-embedded serial placental sections from 24 normotensive (NC) and 19 women with PE, using antibodies to cav-1, prorenin receptor (PRR), angiotensinogen (AGT), AT1R, AngII type 2 receptor (AT2R) and eNOS. Protein expression was semi-quantitatively assessed and also analysed with respect to previously measured maternal plasma TBARS (Thiobarbituric acid-reactive substances) concentration and placental glutathione peroxidase (GPx) activity. Results Positive correlations were observed between placental expression of cav-1 and the AT2R ( P = 0.003) and PRR ( P P > 0.7, P > 0.5). However, cav-1 was inversely correlated with eNOS expression in both NC and PE placentae ( P P = 0.003). No significant correlations were observed with AGT or AT1R. A negative correlation was observed between maternal TBARS and cav-1 protein ( P = 0.003), and between placental GPx activity and cav-1 protein ( P = 0.027) only in the PE placentae. Conclusions A complex cascade links activation of the AT1R with NADPH oxidase activation, generation of reactive oxygen species (ROS), the uncoupling of eNOS and subsequent modification of redox-sensitive caveolar proteins in vascular smooth muscle outside pregnancy. Our findings suggest that this cascade is altered in hypertensive pregnancy, in a direction which would lead to enhanced local vasoconstriction.