Abstract

Introduction Pre-eclampsia (PE), increases the risks of later cardiovascular disease possibly through endothelial dysfunction. Atherosclerosis has been associated with low cholesterol efflux from peripheral macrophages to HDL particles. We hypothesise that there is a link to atherosclerosis via impaired cholesterol flow and thus future cardiovascular risk. Objective We measured cholesterol efflux capacity, apoA1 and apoE, in maternal plasma at 6-8 weeks postpartum from women who had undergone a normotensive pregnancy (NC; n =23) or had experienced PE ( n =67). Methods Cholesterol efflux was performed in RAW264.7 cells with maternal plasma of NC or PE pregnancies as acceptor. ApoA1 and apoE were measured by ELISA. Results Maternal cholesterol efflux capacity was reduced in PE compared to NC (% cholesterol efflux; median [IQR]; NC: 114.7 [107, 127.9]; PE: 108.8 [95.7, 121.6]; P =0.02). ApoE concentrations were also reduced in these women (median [IQR]; NC: 7.02 [5.85, 8.10]; PE: 5.39 [3.94, 7.37]g/L; P =0.004). However, no differences were observed in apoA1 concentrations ( P >0.05). When the PE data were analysed by onset of disease (early-onset before 34 weeks and late-onset after 34 weeks), the late-onset PE group had significantly lower cholesterol efflux compared to the early-onset PE group ( P =0.03). Conclusions Decreased maternal cholesterol efflux capacity persists 6–8 weeks following PE. A decrease in the key step in reverse cholesterol transport, coupled with reduced apoE concentrations, suggest a disruption in cholesterol homeostasis increasing the probability of future cardiovascular disease. The further reduction in the late-onset PE group implies that these women may have had pre-existing metabolic disease/endothelial dysfunction that only manifests following the stress test of pregnancy. Further work is required to validate these initial findings.

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