Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 3 of 3
Full-Text Articles in Entire DC Network
Epigenetic Regulation Of Genes Involved In Vascular Dysfunction In Preeclamptic Women, Ahmad Mousa
Epigenetic Regulation Of Genes Involved In Vascular Dysfunction In Preeclamptic Women, Ahmad Mousa
Theses and Dissertations
DNA methylation is the most recognizable epigenetic mechanism. In general, DNA hypomethylation is associated with increased gene expression whereas DNA hypermethylation is associated with decreased gene expression. To date, little is known about the role of DNA methylation in the pathophysiology of preeclampsia. In this study, we examined the differences in DNA methylation in omental arteries of normal pregnant and preeclamptic women using the high throughput Illumina HumanMethylation27 BeadChip assay. We found 1,685 genes with a significant difference in DNA methylation at a false discovery rate of < 10% with many inflammatory genes having reduced methylation. The thromboxane synthase gene was the most hypomethylated gene in preeclamptic women as compared to normal pregnant women. When we examined the expression of thromboxane synthase in omental arteries of normal pregnant and preeclamptic women we found it to be significantly increased in preeclamptic women. The increased expression was observed in vascular smooth muscle cells, endothelial cells and infiltrating neutrophils. Experimentally induced DNA hypomethylation increased the expression of thromboxane synthase in the neutrophil-like HL-60 cell line, whereas tumor necrosis factor α (TNFα), a neutrophil product, increased its expression in cultured human vascular smooth muscle cells (VSMC). These finding suggest that DNA methylation and release of TNFα by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in systemic blood vessels of preeclamptic women, contributing to the hypertension and coagulation abnormalities. We also explored the possible contribution of DNA methylation to the altered expression of genes involved in collagen metabolism in preeclampsia. Several matrix metalloproteinase (MMP) genes, including MMP1 and MMP8, were significantly less methylated in preeclamptic women, whereas TIMP and COL genes were either significantly more methylated or had no significant change in their DNA methylation status. Experimentally induced DNA hypomethylation increased the expression of MMP-1, but not TIMP-1 or COL1A1, in cultured VSMCs and increased the expression of MMP-1 and MMP-8 in HL-60 cells. These findings suggest that DNA methylation contributes to the imbalance in genes involved in collagen metabolism in blood vessels of preeclamptic women.
Neutrophil Products Control The Expression Of Progesterone Receptors And Matrix Metalloproteinase-1 In The Decidual And Myometrium And Are Possible Regulators Of Premature Labor, Anna Solotskaya
Theses and Dissertations
Neutrophils infiltrate myometrium and decidual tissue prior to parturition. Activated neutrophils release reactive oxygen species (ROS) and tumor necrosis factor α (TNFα), which might increase expression of pro-labor genes such as matrix metalloproteinase-1 (MMP-1), progesterone receptor (PR) A/B ratio, and cause demethylation of DNA. These changes might cause labor. Decidual tissue was obtained from consented, healthy women at term (37+ weeks of gestation) not in labor (no contractions, without cervical effacement), term labor and preterm labor (under 37 weeks of pregnancy). Decidual and myometrial cells in culture were treated with (1) ROS, (2) TNFα, or (3) 5-aza-2’-deoxycytidine. Total RNA was …
Functional Consequences Of Matrix Metalloproteinase-1 Over-Expression In Human Gliomas, Emily Mullet
Functional Consequences Of Matrix Metalloproteinase-1 Over-Expression In Human Gliomas, Emily Mullet
Theses and Dissertations
Malignant brain tumors are among the deadliest of human cancers. Despit recent advancements in conventional therapies, glioblastomas remain incurable, largel y due to their ability to invade surrounding tissue. Matrix metalloproteinases are thought to contribute to the invaseive phenotype of human gliomas. Absent in normal brain, matrix metalloproteinase-1 (MMP-1) has been shown to be present in gliomas, and in particular in glioblastoma multiforme (GBM). To begin to examine the role of MMP-1 in these tumore, two human glioma cell lines were stably transfected with MMP-1 cDNA. Confirmation of MMP-1 over-expression in these cells was achieved through real-time PCR and Western …