Effects of pre-eclampsia on HDL-mediated cholesterol effiux capacity after pregnancy

Background and aims: Preeclampsia (PE) is associated with life-long increased risk of cardiovascular disease. One of the main protective functions of high-density lipoprotein (HDL) is its role in reverse cholesterol transport. HDL-mediated cholesterol effiux capacity (CEC) is decreased during pregnancy in women with PE. Whether this persists postpartum is unknown. Methods: Basal and transporter-specific CEC were determined 6 months postpartum in women who had a normotensive (n = 44) or a PE (n = 42) pregnancy. CEC was also measured in 23 normotensive and 20 PE women for whom samples were collected 24 months postpartum. Basal, ATP-binding cassette transporter-A1 (ABCA1)-and-G1 (ABCG1)-specific CEC were primarily determined using Chinese hamster ovary cells stably expressing human ABCA1 or ABCG1, and were also assessed using a J774 mouse macrophage cell line. Results: ABCA1-specific CEC was significantly lower in women who had PE 6 months postpartum (0.57 +/- 0.1 vs 0.53 +/- 0.08; p < 0.05), whilst basal and ABCG1-specific effiux were not significantly different. cAMP-specific CEC in J774 cells was also lower 6 months after PE (0.85 +/- 0.21 vs 0.75 +/- 0.25, p < 0.05). Although apoA-I, apoE, plasminogen and PON-1 levels were not significantly different in women who had PE compared with controls, ABCA1 effiux did correlate with apoA-l, HDL-C and apoE levels after a normal, and with apoA-l and HDL-C levels after a PE pregnancy. ABCA1-specific effiux decreased in all women between 6 and 24 months postpartum, by 11 +/- 1.6% in women who had a normotensive pregnancy and 9 +/- 1.3% in women who had PE. After adjustment for apoA-I levels, there was no significant difference in ABCA1-specific effiux between the groups at 6 months postpartum and in normotensive women over time, but remained significantly different between 6 and 24 months in women who had PE. Conclusions: ABCA1-mediated CEC is impaired 6 months postpartum after a PE pregnancy and decreases thereafter in both normotensive and PE pregnancies. ABCA1-mediated effiux is dynamic after pregnancy but is unlikely to explain the long-term increased CVD risk in women with PE. (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

After hypertensive pregnancy, ABCA1-mediated HDL cholesterol efflux capacity is impaired and continues to decrease postpartum. However, this decrease is unlikely to explain the long-term increased risk of cardiovascular disease in women with hypertensive pregnancies.