Abstract 21487: A Translational Proteomics Analysis of the Blood-Tissue Interface in the Vascular Bed of the Mouse Placenta Identifies Markers of Human Vascular Diseases
Introduction: Early development of the cardiovascular system is crucial to early embryogenesis. The largest source of vascular genesis errors in human development is during placentation. The placenta is a vital organ, necessary for the survival of mammalian embryos and placental dysfunction is believed to be the major cause of two of the most serious complications of pregnancy, severe early-onset maternal preeclampsia (PE) and fetal intra-uterine growth restriction (IUGR). Here, we systematically documented for the first time the vascular surface-associated proteome of the fetal and maternal vasculature of micro-dissected labyrinth tissue from mice.
Methods and Results: Silica-bead coating in combination with MudPIT-based proteomics and parallel microarray analyses identified 3,444 vascular surface enriched proteins of the mouse labyrinth. Interestingly, direct comparison of the fetal and maternal vascular proteome identified 3,087 proteins in the maternal trophoblasts and 2,497 proteins associated with the fetal endothelium, with the majority of the proteins (∼ 62%) shared among both vasculatures. We then applied rigorous machine-learning algorithm to select proteins likely expressed in the plasma membrane compartment, while the second objective was to identify proteins differentially expressed between the maternal and fetal lumens. This identified 171 maternal and 192 fetal vasculature proteins. Through integrated data mining we identified 14 novel candidate markers at the maternal surface (i.e. trophoblast markers) that exhibited increased expression in pathological human placentas. We validated two, membrane metallo-endopeptidase (MME) and G-protein subunit alpha-12 (GNA12), by quantitative Western blots in a panel of 43 human placentas with clinical annotation.
Conclusions: These data elucidated plasma membrane localized proteins that could be used as imaging probes or diagnostic biomarker. We further identified 14 trophoblast biomarkers that showed changes in protein expression in human pathological pregnancies associated PE and IUGR. We validated two of these markers; GNA12 and MME protein both showed increased expression in 32 out of 33 patient samples with abnormal placental pathology.
- © 2010 by American Heart Association, Inc.