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dc.contributor.advisorChang, Jiang
dc.creatorYang, Tingli
dc.date.accessioned2019-01-16T19:35:18Z
dc.date.available2019-12-01T06:33:25Z
dc.date.created2017-12
dc.date.issued2017-12-14
dc.date.submittedDecember 2017
dc.identifier.urihttp://hdl.handle.net/1969.1/173133
dc.description.abstractHigh-fat diet (HFD)-induced obesity is a risk factor contributing to cardiovascular disease. Excessive accumulation of fatty acids in the heart can cause cardiac dysfunction and heart failure and is referred to as lipotoxic cardiomyopathy. A number of pathological conditions can create this lipotoxic environment in the heart, such as obesity, insulin resistance, and diabetes mellitus. The deleterious effects of hyperlipidemia on the heart are well recognized. Many signaling pathways associated with cardiac lipotoxicity have been suggested. However, there is limited insight into the epigenetic signaling mechanism of the heart in response to excessive fatty acids preceding metabolic and vascular disorders, and the associated epigenetic mechanisms promote lipotoxic cardiomyopathy. Therefore, the main purpose of this study is to delineate the initial epigenetic signaling mechanism in response to lipid overload and define its contribution to lipotoxic cardiomyopathy. In our mouse model, we found that the animals that have been fed with high fat diet (60% kcal) for 2 weeks are predisposed to hemodynamic stress (transverse aortic constriction) with an increase of miR-23a and miR-23b expression levels. Also, these 2 miRs target on a histone lysine 36 methyltransferase called Setd2 and repress its expression, which might cause the cardiomyopathy predisposed phenotype. In vivo, we identified the above hypothesis by using Setd2 cardiac specific haploinsufficiency mice and Setd2 cardiac-specific transgenic mice. In conclusion, we observed that high fat diet caused heart predisposed to hypertrophy through upregulation of miR-23a and miR-23b, and repress Setd2.en
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.subjecthigh fat dieten
dc.subjectlipotoxic cariomyopathyen
dc.subjectmicroRNAen
dc.subjecthistone modifieren
dc.titleMECHANISTIC STUDY OF HIGH FAT DIET-INDUCED CARDIOMYOPATHYen
dc.typeThesisen
thesis.degree.departmentCollege of Medicineen
thesis.degree.disciplineMedical Sciencesen
thesis.degree.grantorTexas A & M Universityen
thesis.degree.nameDoctor of Philosophyen
thesis.degree.levelDoctoralen
dc.contributor.committeeMemberSchwartz, Robert
dc.contributor.committeeMemberDavies, Peter
dc.contributor.committeeMemberLin, Xia
dc.contributor.committeeMemberZhou, Yubin
dc.type.materialtexten
dc.date.updated2019-01-16T19:35:18Z
local.embargo.terms2019-12-01
local.etdauthor.orcid0000-0002-4327-9916


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