Anti-diabetic therapy based on the incretin hormone glucagon-like peptide-1 (GLP-1) and GLP-1 reduce formation of aortic aneurysms in animal models, while experimental and clinical data support effects of GLP-1 on the molecular mechanisms involved in thoracic aortic aneurysm (TAA).
TAA develops slowly without symptoms into life threatening conditions, there are no screening programs or pharmaceutical interventions, but treatment is restricted to surgery. We aim to further our understanding of; if and how incretin therapy/GLP-1 contributes to the reduced prevalence of TAA in diabetes. Knowledge gained may provide means of identifying patients for computer tomography to detect possible TAA formation, while also facilitating the first pharmacological interventions to prevent small TAAs from progressing into life threatening conditions.
GLP-1, Th1/Th2 cytokines, protease activity, oxidative stress etc. are analyzed in plasma from diabetic/non-diabetic patients with aortic valve pathology and w/wo TAA, included in ongoing clinical studies. Biopsies are obtained during surgery and aortic wall proteolytic activity/collagen composition determined. Associations between GLP-1 and mediators of TAA progression/formation are determined. This master thesis project focuses on further investigating observed associations between GLP-1 and mediators of TAA formation/progression using in vitro models.
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