{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/1219"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/1219","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs","abstract":"The 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.","abstract_html":"The 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.","abstract_has_math":false,"creators":["Johnson, Brett A."],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Olson, Eric N."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-01-16T21:07:45Z","date_published":"2013-01-16T21:07:45Z","updated_at":"2026-07-24T05:52:20Z","subjects":["MicroRNAs","Heart","Exercise"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["828671955"],"render_values":[{"text":"828671955","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/1219","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Olson, Eric N."]},{"key":"dc:creator","label":"Author","values":["Johnson, Brett A."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-01-16T21:07:45Z","2013-01-16"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["MicroRNAs","Heart","Exercise"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/1219","828671955"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The 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."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs"]}]}],"canonical_facts":{"dc:contributor":["Olson, Eric N."],"dc:creator":["Johnson, Brett A."],"dc:date":["2013-01-16T21:07:45Z","2013-01-16"],"dc:description":["The 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."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/1219","828671955"],"dc:language":["en"],"dc:subject":["MicroRNAs","Heart","Exercise"],"dc:title":["Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs"],"dc:type":["Thesis","Text"]},"updated_at":"2026-07-24T05:52:20Z"}