The Effects of LCN2 and Iron on Cardiac Remodeling and the Impact on Cardiac Function

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dc.contributor.advisorSweeney, Gary
dc.creatorSung, Hyekyoung
dc.date.accessioned2018-03-01T14:04:05Z
dc.date.available2018-03-01T14:04:05Z
dc.date.copyright2017-08-10
dc.date.issued2018-03-01
dc.date.updated2018-03-01T14:04:05Z
dc.degree.disciplineBiology
dc.degree.levelDoctoral
dc.degree.namePhD - Doctor of Philosophy
dc.description.abstractLipocalin-2 (Lcn2; also termed neutrophil gelatinase-associated lipocalin (NGAL)) is a proinflammatory factor which is elevated in obese individuals. It has also been implicated in the pathogenesis of heart failure and as a potential biomarker. This thesis exaimed: project 1: Regulation of autophagy by Lcn2 and its functional significance in leading to insulin resistance in cardiomyocytes, project 2: Changes in cardiac function, autophagy and cell death in wild type and Lcn2-knockout mice subjected to chronic myocardial ischemia, and project 3: Effect of iron on insulin sensitivity in cardiomyocytes and mechanistic role of oxidative stress. Findings from project 1 indicated that Lcn2 treatment caused insulin resistance and use of gain and loss of function approaches elucidated a causative link between autophagy inhibition and regulation of insulin sensitivity in response to Lcn2. Project 2 data demonstrated that Lcn2 attenuated autophagy to worsen the extent of apoptosis induced by chronic myocardial ischemia in mice. Finally, in project I showed that iron directly induced insulin resistance in cardiomyocytes and that this involved regulation of the crosstalk between autophagy and oxidative stress. In summary, my studies demonstrated that Lcn2 promoted cardiac dysfunction and that lack of Lcn2 in mice was protective against surgically-induced heart failure. Inhibition of autophagy played a central mechanistic role in mediating the detrimental effects of Lcn2 on the heart, which included elevated oxidative stress, cell death and insulin resistance.
dc.identifier.urihttp://hdl.handle.net/10315/34355
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectBiology
dc.subject.keywordsLipocalin-2
dc.subject.keywordsAutophagy
dc.subject.keywordsHeart failure
dc.subject.keywordsInsulin resistance
dc.subject.keywordsIron
dc.subject.keywordsApoptosis
dc.subject.keywordsOxidative stress
dc.titleThe Effects of LCN2 and Iron on Cardiac Remodeling and the Impact on Cardiac Function
dc.typeElectronic Thesis or Dissertation

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