Figure 5

Proposed mechanism linking dysregulation of the renin-angiotensin system (RAS), with inadequate selenium and antioxidant protection, leading to pre-eclampsia. Poor implantation, inadequate evtravillous trophoblast invasion and resultant poor placental perfusion could lead to dysregulation in the RAS. The RAS has been closely linked to the formation of excessive amounts of free radicals and thus breakdown of the mitochondrial reduction–oxidation balance. This extra free radical production, with the known reduced selenium and reduced antioxidant glutathione peroxidase (GPx) activity in pre-eclampsia will result in increased placental and circulating oxidative stress. This oxidative state is proposed to enhance the conversion of AGT in the maternal circulation to the more active oxidized form. The oxidized form of AGT, compared to the reduced form, interacts with renin with four-fold higher binding affinity resulting in increased generation of angiotensin I, and hence the potent vasoconstrictor angiotensin II (Ang II) in the presence of similar absolute AGT concentrations. Finally, this further disrupts the RAS as well as alters downstream antiangiogenic makers through increased sFLt-1 and reduced placental growth factor (PLGR), culminating the in the clinical manifestation of pre-eclampsia.