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dc.contributor.authorTra, John
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2011-06-20 13:59:48.473en
dc.date.accessioned2011-06-20T18:26:38Z
dc.date.available2011-06-20T18:26:38Z
dc.date.issued2011-06-20T18:26:38Z
dc.identifier.urihttp://hdl.handle.net/1974/6564
dc.descriptionThesis (Ph.D, Biochemistry) -- Queen's University, 2011-06-20 13:59:48.473en
dc.description.abstractElevated plasma concentrations of lipoprotein(a) (Lp(a)) are a risk factor for a variety of atherosclerotic disorders including coronary heart disease. In the current study, the investigators report that incubation of cultured human umbilical vein endothelial cells (HUVECs) with high concentrations of apolipoprotein(a)(apo(a)/Lp(a)) induces apoptosis and endothelial dysfunction in a dose dependent manner. Apo(a), the component of Lp(a) mediates these effects by inducing externalization of Annexin V, DNA condensation and fragmentation which are the hallmarks of death by apoptosis. The pathway of apo(a)-induced apoptosis is associated with overexpression of Bax, caspase-9, p53 phosphorylation, decreased in Bcl-2 expression and activation of caspase-3. Taken together, the data suggest that elevated concentration of apo(a) induces apoptosis in endothelial cells probably by activating the intrinsic pathway. The data also showed that apo(a) induces increased expression of the growth arrest protein (Gas1), which has been known to induce apoptosis and growth arrest in vitro. In addition the data showed that elevated apo(a)/Lp(a) attenuates endothelial nitric oxide (eNOS) activity and endothelin-1 (ET-1) in a dose and time-dependent manner, particularly with small apo(a) isoforms. In summary, the authors proposed a new signaling pathway by which apo(a)/Lp(a) induce apoptosis and this finding could help explain how apo(a)/Lp(a) mediate atherosclerosis related diseases.en
dc.languageenen
dc.language.isoenen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectApolipoprotein(a)en
dc.subjectApoptosisen
dc.subjectLipoprotein(a)en
dc.titleApoliprotein(a)-Induced Apoptosis in Vascular Endothelial Cellsen
dc.typethesisen
dc.description.degreePh.Den
dc.contributor.supervisorKoschinsky, Marlysen
dc.contributor.departmentBiochemistryen


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