Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 118-138). Available also in a digital version from Dissertation Abstracts.

Thesis (M.A.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains ix, 60 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 29-34).

Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 15, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Gabor Forgacs. Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 118-145). Also available in print.

Thesis (Ph.D)--Civil and Environmental Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Haj-Ali, Rami; Committee Member: White, Donald; Committee Member: Will, Kenneth; Committee Member: Yavari, Arash; Committee Member: Yoganathan, Ajit. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Includes bibliographical references (p. 64-65).

published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Public Health / Master / Master of Public Health

Obesity is closely related to many medical complications such as type 2 diabetes, hypertension and heart failure. Obesity and other factors, including elevated blood glucose levels, hypertension, and dyslipidemia, constitute a constellation of symptoms known as the metabolic syndrome, which are the risk factors for coronary artery disease. Lipocalin-2 is a pro-inflammatory adipokine causally involved in the development of obesity-associated metabolic and cardiovascular diseases. Recent clinical and experimental evidences demonstrate an association between augmented circulating lipocalin-2 and cardiac dysfunction. However, little is known about the detailed roles of lipocalin-2 in regulating pathophysiological functions of the heart. The present study was designed to compare the heart functions of mice with normal (WT) or deficient lipocalin-2 (Lcn2-KO) expression and to examine the molecular mechanisms underlying lipocalin-2-mediated deteriorated effects in hearts. Echocardiographic analysis revealed that the myocardial contractile function was significantly improved in hearts of Lcn2-KO mice, under both standard chow and high fat diet conditions. The heart function before and after I/R injury (20-min of global ischemia followed by 60-min of reperfusion) was assessed using the Langendorff perfusion system. Compared with WT littermates, hearts from Lcn2-KO mice showed improved functional recovery and reduced infarct size following I/R. These phenomena can be observed in mice under both standard chow and high fat feeding conditions. Under baseline condition, the mitochondrial function of hearts from Lcn2-KO mice was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity, markers of biogenesis and oxidative stress, as well as electron microscopic investigation of the mitochondrial ultrastructure. Acute or chronic administration of lipocalin-2 impaired cardiac functional recovery to I/R and dampened the mitochondrial function in hearts of Lcn2-KO mice. These effects were associated with an extensive modification of the fatty acyl chain compositions of intracellular phospholipids. In particular, lipocalin-2 facilitated the redistribution of linoleic acid (C18:2) among different types of phospholipid, including cardiolipin, which is exclusively located in the mitochondria inner membrane. The direct effects of lipocalin-2 on both H9c2 and NCM cells were also examined. TUNEL assay and flow cytometry analysis demonstrated that lipocalin-2 treatment promoted apoptosis in cardiomyocytes. Lipocalin-2 induced an early phase of phosphatidylserine exposure, followed by Bax-translocation and caspase-3 cleavage. The results collectively suggested that lipocalin-2 initiated the intrinsic mitochondria-mediated apoptotic pathway. In the hearts of Lcn2-KO mice, significantly reduced number of apoptotic cells was observed after I/R injury. In conclusion, lacking of lipocalin-2 improved heart function recovery during I/R injury via mitochondrial function restoration, phospholipids remodeling, and inhibition of cardiomyocytes apoptosis. / published_or_final_version / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy