PP018. Does altitude affect the placental renin angiotensin system (RAS) in pre-eclampsia (PE)?

INTRODUCTION

We have previously shown the activation of placental RAS in high altitude normotensive (NT) pregnancies [1], presumably related to hypoxia during placental development. PE incidence is increased at high altitude; hypoxia-reoxygenation injury contributes to the elevated oxidative stress seen in this condition. Binding of Angiotensin II to its type I receptor (AT1R) increases generation of reactive oxygen species and we have shown an increase in AT1R in PE [2]. Therefore we investigated whether the RAS is further augmented in PE at high altitudes.

METHODS

Biopsies were collected, with informed, written consent, from NT and PE women (ISSHP guidelines) at sea-level (UK) and high altitude, 3100m (Leadville, Colorado) immediately after vaginal delivery or elective non-laboured Caesarean section. mRNA expression of the RAS components (angiotensinogen (AGT), prorenin, prorenin receptor, AT1R and angiotensin type 2 receptor) was determined by qRT-PCR and normalised to 3 stably-expressed housekeeping genes using geNorm. Protein expression was semi-quantitatively assessed by immunohistochemistry (H score) and compared between groups (Mann Whitney U test).

RESULTS

mRNA expression of all RAS components was unaffected by altitude in NT, but significantly lower for all in PE (P=0.026-<0.0001). However, in NT, protein expression of all components except AGT was significantly increased at altitude (P=0.037-<0.001). Protein expression of AGT and AT1R was also increased in altitude PE (P<0.004 for both).

CONCLUSION

We have shown the placental RAS to be activated at altitude, with apparent differences in transcription/translation. Hypoxia-inducible transcription factors such as HIF-1 enhance transcription and translation of many genes encoding "rescue" proteins; this might explain the effects of altitude in NTs. HIF-1 is increased in PE, which might allow increased protein expression at altitude in spite of lower mRNA.