The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals these processes are usually associated with poor vascular function. However maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma high density lipoprotein (HDL), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vaso-dilatory, anti-oxidant, anti-thrombotic and anti-inflammatory effects and can protect against endothelial cell damage. In pregnancy, plasma HDL concentration starts to rise at 10 weeks' gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesised around the time of the establishment of the feto-placental circulation. In obese pregnancy and to a greater extent in preeclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesise that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in preeclampsia this fails to occur. 242 words

Objective: High-density lipoprotein (HDL) has well-established anti-atherosclerotic properties in the non-pregnant population. HDL may have a potential role in protecting maternal vascular function during pregnancy that fails to occur in preeclampsia. HDL function is determined by its protein and lipid composition. This study aimed to examine protein composition of HDL at different gestations throughout healthy pregnancy and to compare HDL proteome in the third trimester of healthy pregnancy and preeclampsia. Design and method: HDL was isolated from two cohorts of n = 10 healthy pregnant women at 8 different timepoints throughout pregnancy; pre-pregnancy, week 4.6, week 6.1, week 8.4, (cohort 1) and week 15, week 25, week 35 and 3 months post-natal (cohort 2), and from healthy pregnant (n = 10) and preeclampsia (n = 6) women at the third trimester. The proteome of HDL was measured by nano liquid chromatography coupled to tandem mass spectrometry (nLC-MS/MS). Results: There were 16 proteins in HDL that showed significant differences throughout healthy pregnancy which were apolipoprotein A-IV, apolipoprotein C-II, apolipoprotein C-III, apolipoprotein C-IV, apolipoprotein F, apolipoprotein L-I, angiotensinogen, alpha-1-acid glycoprotein 2, alpha-1-antitrypsin, cathelicidin antimicrobial peptide, fibrinogen alpha chain, fibrinogen beta chain, prenylcysteine oxidase 1, serum amyloid a-I, serum paraoxonase/lactonase 3 and vitronectin. In preeclampsia, HDL apolipoprotein A-I was lower than healthy pregnancy, while HDL alpha-1-antitrypsin, pigment epithelium-derived factor and vitamin D-binding protein were higher. Conclusions: There were significant differences in the protein composition of HDL during pregnancy and between healthy pregnancy and preeclampsia in the third trimester. These compositional differences may be involved in HDL function and may indicate HDL's role in vascular protection in pregnancy.