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dc.contributor.authorMoratin, Jordan
dc.date.accessioned2023-08-03T18:11:09Z
dc.date.available2023-08-03T18:11:09Z
dc.date.issued2023-05
dc.identifier.urihttp://hdl.handle.net/10675.2/624723
dc.descriptionThe file you are attempting to access is restricted to Augusta University. Please login using your JagNet iD and password.en_US
dc.description.abstractCardiovascular disease remains the number one cause of mortality in humans. An important influence in the progression of artery disease is the long-term effect of disruptions in daily patterns or circadian rhythms. Not sleeping well at night, and daytime sleepiness associate with cardiovascular disease. In addition, a cardiovascular system that does not rest well at night is also bad. A blood pressure reading that does not decrease at night called non-dipping hypertension worsens cardiovascular disease. One important impact of broken rhythms is to cause disease in arteries. Thus, understanding the mechanisms that control 24-hour daily patterns is important. One key component gene of circadian rhythm is the transcription factor Bmal1. Vascular disease is a progression that begins as an adaptation to hypertension, diabetes, and hypercholesterolemia, whereby blood vessels change their structure in response to these changes in the bloodstream through a process called vascular remodeling. Remodeling is a process whereby arteries, arterioles, and even veins change their size and cellular structure (muscularity). Using mouse models of genetic disruption, our lab previously found that Bmal1 has an important role to control vascular remodeling, and when Bmal1 is disrupted, a vascular disease phenotype occurred. The lab also found that the endothelial cell layer of arteries contributes to the disease in Bmal1 knockout (KO) mice. These observations seemed the same in both males and females, thus, were sex independent. Bmal2, is a paralog of Bmal1, and interacts with Bmal1, and is more selectively expressed in the endothelium. However, the role of Bmal2 in remodeling is not clear. To understand the role of Bmal2 in vascular disease, I have implemented a widely used experimental animal model of arterial ligation to induce vascular remodeling. I have ligated the left common carotid artery (LC) in two groups of mice, control wild-type mice (no genetic mutation) and the experimental Bmal2-KO (global knockout) mice. After two weeks, I isolated the LC and fixed the arteries in optimal cutting temperature (O.C.T.) compound and conducted histological processing (cut cross sections with a cryotome and staining with hematoxylin and eosin). I then quantified the changes in structure in the artery using the ImageJ program on digitized microscope images. My findings show that inward remodeling and wall-hypertrophy in male Bmal2-KO mice are similar to wild-type mice. The inward remodeling observed in the male WT and male Bmal2-KO mice is consistent with the normal response of what has been observed in this ligation model, inward accompanied by wall hypertrophy. However, I saw something different in the female Bmal2 KO mice undergoing the ligation for two weeks. Female Bmal2-KO mice exhibited robust inward remodeling that was accompanied by intimal hyperplasia. My data suggest that there are sex-specific differences in remodeling controlled by Bmal2.en_US
dc.language.isoen_USen_US
dc.publisherAugusta Universityen_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.titleThe role of bHLH transcription factor Bmal2 in arterial endothelialcircadian rhythms and remodeling: Sex dependent effects in miceen_US
dc.typeThesisen_US
dc.contributor.departmentCell and Molecular Biologyen_US
dc.description.advisorRudic, Dan
dc.description.committeeRudic, Dan; Wilson, Christina; Curry-McCoy, Tiana


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