Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent molecular mechanisms in the origins of this disease.
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PMID:Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia. 2198 93

Preeclampsia, characterized by high blood pressure, albuminuria and other systemic disorders, is a serious complication during pregnancy. It has been reported that GNA12 is overexpressed during preeclampsia. In this study, we investigated the potential association between the methylation of the GNA12 promoter and preeclampsia. The methylation level at eight CpG sites of the GNA12 promoter was analyzed by MassARRAY in placenta and peripheral blood DNA samples from 50 preeclampsia patients and 50 normal pregnant women. In the placenta DNA samples, the methylation level at three CpG sites of the GNA12 promoter was significantly lower in the preeclampsia patients than in the controls. The difference was also significant at two of the three CpG sites in the peripheral blood DNA samples. The mRNA expression level of GNA12 in placenta was analyzed by real-time quantitative PCR in 20 cases and 20 controls. Consistent with the decreased methylation level, the mRNA expression level of GNA12 was higher in preeclampsia patients than in controls. Our results showed that preeclampsia is associated with decreased methylation of the GNA12 promoter, which can be detected in both the placenta and the peripheral blood of the pregnant women.
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PMID:Preeclampsia is Associated with Decreased Methylation of the GNA12 Promoter. 2676 93