Examining The Role Of Lysyl Oxidase Enzymes In Atrial Fibrillation Induced By Volume Overload

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dc.contributor.advisorBackx, Peter
dc.contributor.authorSherrard, Dana Evelyn
dc.date.accessioned2025-04-10T10:45:49Z
dc.date.available2025-04-10T10:45:49Z
dc.date.copyright2024-08-06
dc.date.issued2025-04-10
dc.date.updated2025-04-10T10:45:49Z
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractAtrial fibrillation (AF), the most prevalent cardiac arrhythmia, is linked to atrial electrical and structural remodelling. AF is associated with fibrosis; however, in models imposing atrial stretch, this occurs without changes in collagen transcription, suggesting fibrosis results from collagen stabilization by the Lysyl Oxidases (LOX) family of enzymes. To investigate this relationship, we established a murine aortic regurgitation (AR) model, which induces atrial stretch. AR mice exhibited increased AF susceptibility, decreased atrial refractoriness (AERP), elevated left atria (LA) fibrosis, and macrophage infiltration 2-fold compared to sham mice. LOXL2 inhibitor PXS-5382 reduced AF inducibility, shortened AF duration and attenuated fibrosis without affecting AERP. In contrast, the broader LOX inhibitor PXS-5505 prevented fibrosis without reducing AF inducibility in AR mice but exacerbated AF and fibrosis in sham mice. These results highlight LOXL2's critical role in atrial structural remodelling and AR-induced AF, suggesting it may be a promising therapeutic target for AF.
dc.identifier.urihttps://hdl.handle.net/10315/42779
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subject.keywordsAtrial Fibrillation
dc.subject.keywordsFibrosis
dc.subject.keywordsLysyl oxidase
dc.subject.keywordsAortic regurgitation
dc.subject.keywordsEndurance training
dc.subject.keywordsArrhythmias
dc.titleExamining The Role Of Lysyl Oxidase Enzymes In Atrial Fibrillation Induced By Volume Overload
dc.typeElectronic Thesis or Dissertation

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