The Role of Sodium-Calcium Exchanger in the Regulation of Endothelial Function

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atmire.migration.oldid3012
dc.contributor.advisorCole, William
dc.contributor.authorLiao, Chiu-Hsiang
dc.date.accessioned2015-02-25T21:39:27Z
dc.date.embargolift10000-01-01
dc.date.issued2015-02-25
dc.date.submitted2015en
dc.description.abstractAppropriate release of nitric oxide (NO) is critical for normal physiological functioning of the cardiovascular system. Although a rise in intracellular Ca2+ concentration ([Ca2+]i) in endothelial cells (ECs) is thought to play an important role in the coordination of NO release, the molecular mechanism underlying this influx is poorly understood. The work presented here outlines the molecular mechanisms responsible for regulating endothelial [Ca2+]i and its implication to NO production and release, and involved two major areas of study. Firstly, we identified the presence of a signaling complex comprised of stromal interaction molecule 1 (STIM1), transient receptor potential protein (canonical subtype) 1 (TRPC1), and the Na+/Ca2+ exchanger 1 (NCX1) in cultured ECs, which may be an important component of the Ca2+ influx pathway necessary for the activation of endothelial NO synthase (eNOS) during agonist stimulation. Secondly, recruitment of the NCX in reverse mode was shown to play an important role in flow-mediated dilation and the corresponding phosphorylation of serine-1177 of eNOS (S1177-eNOS). This is the first study to identify S1177-eNOS phosphorylation in response to flow in small (< 300 μm), pressurized, myogenic rat cerebral arteries. These findings are significant because the potential involvement of a TRP-NCX signaling complex in ECs has been an unresolved issue for some time. Therefore the work of this thesis provides unique insight into the molecular mechanisms that contribute to the regulation of endothelial [Ca2+]i.en_US
dc.description.embargotermsindefiniteen_US
dc.identifier.citationLiao, C. (2015). The Role of Sodium-Calcium Exchanger in the Regulation of Endothelial Function (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28353en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/28353
dc.identifier.urihttp://hdl.handle.net/11023/2110
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectPharmacology
dc.subject.classificationEndotheliumen_US
dc.subject.classificationcalciumen_US
dc.subject.classificationSodium-calcium exchangeren_US
dc.titleThe Role of Sodium-Calcium Exchanger in the Regulation of Endothelial Function
dc.typedoctoral thesis
thesis.degree.disciplineCardiovascular & Respiratory Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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