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Title: Investigation of the effects of the glucagon-like peptide-1 mimetic exendin-4 on cardiac remodelling in diabetes
Author: Tate, Mitchel
ISNI:       0000 0004 5367 309X
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2015
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Cardiovascular complications are the leading cause of morbidity and mortality in the global epidemic of diabetes mellitus and despite current diabetic treatment strategies being effective for glycaemic control, the incidence of cardiovascular complications remains significant. Exceptionally, glucagon-like peptide-1 (GLP-1) targeted therapies, which are widely used in the treatment of hyperglycaemia, have been shown to elicit wide-ranging basal physiological cardiovascular effects, and more importantly, they may confer cardioprotective actions against acute myocardial infarction and chronic heart failure in both the presence and absence of hyperglycaemia/diabetes. However, few studies have investigated potential beneficial cardiac actions of GLP-1 targeted therapies in diabetes, due to the inherent difficulty of separating direct effects from those occurring secondary to established metabolic/glucose-lowering actions. Therefore, the aim of this thesis was to study the effects of GLP-1 mimetic, exendin-4, in experimental diabetic cardiomyopathy, with a specific focus on inflammation and the ECM. The findings of this thesis clearly demonstrate that exendin-4 attenuates experimental diabetic cardiac remodelling, at least in part, independently of its established glucose lowering actions, via reduction of myocardial macrophage infiltration and modulation of associated cytokines and chemokines. Specifically, the in vitro findings of this thesis provide strong evidence that the observed beneficial effects of exendin-4 in the diabetic heart may occur secondary to direct actions on infiltrating macrophages, which exert specific paracrine effects on ECM remodelling. These developments are clearly exciting and may have significant implications for the clinical management of both metabolic and cardiovascular diseases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available