Soluble fms-like tyrosine kinase-1 in HIV infected pre-eclamptic South African Black women

Abstract

Introduction: Hypertensive disorders of pregnancy are the commonest direct cause of maternal deaths in South Africa, 83% being attributed to pre-eclampsia. Elevated placental sFlt-1 levels are linked with angiogenic disruption and subsequent pre-eclampsia development. The impact of HIV infection on pre-eclampsia is controversial. Its effect on angiogenic imbalance in both normotensive and pre-eclamptic pregnancies remains unknown.

Methods: We examined the immunolocalisation of both membrane bound and soluble forms of Flt-1, within placentae of HIV negative and positive normotensive and pre-eclamptic pregnancies at term using immunohistochemistry and immuno-electron microscopy.

Results: Strong Flt-1 and sFlt-1 immunoreactivity was observed within endothelial, syncytio and cytotrophoblast cells. Subcellularly, gold particles were localised predominantly within the endoplasmic reticulum and mitochondria and occurring free within the cytoplasm. There was no significant effect of HIV on Flt-1 and sFlt-1 immunoexpression in both exchange and stem villi. A significant effect of type of pregnancy (normotensive vs pre-eclamptic) on Flt-1 and sFlt-1 immunoexpression (p = 0.003) within exchange rather than stem villi, indicated that the pre-eclamptic had elevated Flt-1 and sFlt-1 expressions compared to the normotensive pregnant women. There was no interaction between HIV and pregnancy type (normotensive vs pre-eclampsia) for Flt-1 and sFlt-1 expressions in both exchange and stem villi. A weak correlation of Flt-1 and sFlt-1 intensity between the exchange and stem villi was noted.

Discussion: Elevated immunoexpression of Flt-1 and sFlt-1 within trophoblasts suggests an autocrine mode of action on trophoblast invasion and differentiation thereby contributing to abnormal placentation with consequential endothelial dysfunction in pre-eclampsia.

Conclusion: Irrespective of the HIV status, placental Flt-1 and sFlt-1 expressions remain elevated in pre-eclampsia compared to normotensive pregnancies.

Keywords: Flt-1; HIV; Immunolocalisation; Pre-eclampsia; sFlt-1.