Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs

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dc.contributor.advisorOlson, Eric N.en
dc.creatorJohnson, Brett A.en
dc.date.accessioned2013-01-16T21:07:45Z
dc.date.issued2013-01-16
dc.description.abstractThe heart is an adaptive organ which undergoes pathological or physiological remodeling in response to a variety of stimuli to meet the demands of the body. Chronic exercise training promotes a physiological remodeling response in which the heart increases in size to match loading demands. In this thesis, I present my studies on the function of microRNAs during exercise-induced cardiac remodeling. First, I show the expression of muscle-specific microRNA (miRNA), miR-499, is down-regulated by voluntary free-wheel running in hearts of mice. I hypothesized the reduction of miR-499 may be required for exercise-induced cardiac hypertrophy. I found forced cardiac over-expression of miR-499 was associated with diminished physiological cardiac growth, whereas genetic deletion and antimiR mediated inhibition of miR-499 caused enhanced physiological growth following exercise. I also explored the mechanism by which miR-499 represses exercise-induced cardiac growth. I determined the repressive effects of miR-499 are mediated through regulation of IGF-1/PI-3K/Akt and beta-catenin signaling pathways, which drive physiological growth of the heart. I demonstrated the effects of miR-499 on physiological cardiac growth are mediated, at least in part, through repression of a network of genes including p85-alpha, Rictor, Lin7c and Fzd4. Collectively, the results of my thesis research identify miR-499 as a pivotal regulator of exercise-induced cardiac hypertrophy.en
dc.identifier.oclc828671955
dc.identifier.urihttps://hdl.handle.net/2152.5/1219
dc.language.isoenen
dc.subjectMicroRNAsen
dc.subjectHearten
dc.subjectExerciseen
dc.titleRegulation of Exercise-Dependent Cardiac Growth by MicroRNAsen
dc.typeThesisen
dc.type.materialTexten
thesis.date.available2014-12-21
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineGenetics and Developmenten
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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