High-density lipoprotein (HDL) represents the major cholesterol carrying lipoprotein class in human cord blood, while in maternal serum cholesterol is mainly carried by low-density lipoproteins. Previous findings suggested that HDL isolated from cord blood differs from maternally derived HDL with respect to its proteomic composition, size and function (1, 2). Mass and activity of the HDL associated anti-oxidant enzyme paraoxonase was shown to be 5-fold lower in cord blood, accompanied by very low anti-oxidant capacity of fetal HDL. In line with the impaired anti-oxidative capacity of fetal HDL, our preliminary data suggest profound oxidation of fetal HDL during PE (KMP, CW). Interestingly, maternal HDL appeared to be only minimally affected. Therefore our results indicate that oxidative modified HDL accumulates already during fetal development, and might contribute to fatty streak formation in human fetal aortas. Based on these interesting observations, a PhD student should assess the following aims: (i) Isolation of HDL from maternal and fetal sera (control and preeclampsia), (ii) quantification of the myeloperoxidase fingerprint chlorotyrosine of HDL using mass spectroscopy, identification of apolipoprotein-arginine residues targeted by the reactive carbonyls methylglyoxate and carboxymethllysine, (iii) to determine the impact of PE induced modifications on metrics of HDL function, including HDL cholesterol efflux properties, HDL endothelial regenerative activities (using primary placental endothelial cells), HDL anti-oxidative and paraoxonase activity, HDL mediated anti-inflammatory activities and several enzyme activities involved in HDL maturation and metabolism.
1. Sreckovic I, Birner-Gruenberger R, Obrist B, Stojakovic T, Scharnagl H, Holzer M, Scholler M, Philipose S, Marsche G, Lang U, Desoye G, Wadsack C. Distinct composition of human fetal HDL attenuates its anti-oxidative capacity. Biochim Biophys Acta. 2013 Apr;1831(4):737-46. doi: 10.1016/j.bbalip.2012.12.015.
2.Sreckovic I, Birner-Gruenberger R, Besenboeck C, Miljkovic M, Stojakovic T, Scharnagl H, Marsche G, Lang U, Kotur-Stevuljevic J, Jelic-Ivanovic Z, Desoye G, Wadsack C. Gestational diabetes mellitus modulates neonatal high-density lipoprotein composition and its functional heterogeneity. Biochim Biophys Acta. 2014 Nov;1841(11):1619-27. doi: 10.1016/j.bbalip.2014.07.021.