Figure 2.

The accelerator and brake theory of pre-eclampsia. Schematic diagram to illustrate the sequence of events involved in the pathogenesis of pre-eclampsia. The upstream events consist of dysregulation of endogenous protective pathways – ‘the brakes’ – [CSE which generates H₂S and HO-1 that produces CO] leading to maternal endothelial activation. As a consequence, there is an increase in anti-angiogenic factors – ‘the accelerator’ – (sVEGFR-1, sEng and soluble E-slectin and a decrease in angiogenic factors PlGF and eNOS, which generates NO). These biochemical changes lead to a generalized endothelial dysfunction, renal injury and generation of reactive oxygen species, which precedes the clinical onset of pre-eclampsia. After 20 weeks of gestation, the clinical symptoms manifest themselves as high BP and proteinurea, which are concurrent with excessive inflammation as indicated by increase in pro-inflammatory cytokines (Th1 cytokine production) and ET-1 release.