dc.contributor.advisor | Lovern, Pamela | |
dc.contributor.author | Zhai, Bo | |
dc.date.accessioned | 2019-07-19T14:33:28Z | |
dc.date.available | 2019-07-19T14:33:28Z | |
dc.date.issued | 2018-12-01 | |
dc.identifier.uri | https://hdl.handle.net/11244/320976 | |
dc.description.abstract | Arteriogenesis is the complex process of outward enlargement of small arteries and arterioles, also known as the collaterals. Arteriogenesis involves cell proliferation and vasculature remodeling and it is induced by increased fluid shear stress (FSS) after occlusion in major arteries upstream. Many cell types, including endothelial cells, smooth muscle cells, monocytes, and endothelial progenitor cells, have been implicated in this process. Previous studies indicate that placental growth factor (PLGF) plays a key role in arteriogenesis by acting as both a cell proliferation inducer and a chemoattractant. Previously, our group has shown that PLGF is mainly produced by endothelial cells. Furthermore, using in vitro and ex vivo models, our group was the first to demonstrate that PLGF is upregulated by FSS, and this process is NADPH oxygenase-4 (NOX-4)- and heme oxygenase-1 (HO-1)-dependent. Furthermore, our group discovered iron, a product of HO-1, can upregulate PLGF. In this study, we demonstrate transcription cofactor p300 as a key regulator in PLGF expression. We discovered that FSS upregulates PLGF by increasing transcription, and p300's histone acetyl transferase (HAT) activity is required in this process. This study identifies epigenetic modification as an important aspect in the complex process of arteriogenesis, and provides important insights for future studies and potential pharmaceutical targets of non-invasive treatments for cardiovascular diseases. | |
dc.format | application/pdf | |
dc.language | en_US | |
dc.rights | Copyright is held by the author who has granted the Oklahoma State University Library the non-exclusive right to share this material in its institutional repository. Contact Digital Library Services at lib-dls@okstate.edu or 405-744-9161 for the permission policy on the use, reproduction or distribution of this material. | |
dc.title | Placental Growth Factor Regulation by Shear Stress and Iron Metabolism in Endothelial Cells | |
dc.contributor.committeeMember | Hinsdale, Myron E. | |
dc.contributor.committeeMember | Lacombe, Veronique A. | |
dc.contributor.committeeMember | Clarke, Stephen L. | |
osu.filename | Zhai_okstate_0664D_16060.pdf | |
osu.accesstype | Open Access | |
dc.description.department | Veterinary Biomedical Science | |
dc.type.genre | Dissertation | |
dc.type.material | Text | |