C4A and endothelial dysfunction: Interestingly, recent evidence showed that serum levels of complement fractions implicated in the classical activation pathway such as C1q, C4a, and C4b are decreased in both early and late stages of pre-eclampsia, supporting data from experimental models where C1q has a protective role against pre-eclampsia and C1q deficiency associates with endothelial dysfunction, decreased placental vascular endothelial growth factor, and elevated levels of sFlt-1 [19]; thus, C1q and C4 may prevent the onset of pre-eclampsia [1,2,20,39,40,41].