Characterization of GPR35 in models of cardiac and renal disease

Project Details

G-protein coupled receptor 35 (GPR 35) expression is increased early in the hearts animal models of cardiac disease such as myocardial infarction and models of hypertrophy, and in heart failure patients. Furthermore, in neonatal cardiomyocytes exposed to hypoxia, GPR 35 expression is increased after 12 hours and this increase is mediated by hypoxia-inducible factor 1 (HIF-1). A human polymorphism for this receptor has been identified and is associated with high coronary artery calcification, a measure of subclinical coronary atherosclerosis, which has been used to predict coronary artery disease events.  Evidence suggests that GPR35 may be an early marker of cardiac pathology and may also be a potential target for the development of novel therapies. We have recently identified increased GPR 35 expression in the heart and kidney in respective models of chronic cardiac and renal disease.

This project will assess the expression of GPR 35 in archived tissues from various animal models of cardiac and renal disease, including myocardial infarction, diabetes and chronic kidney disease using immunohistochemistry, western blot analysis and real time PCR. Cell culture experiments activating GPR 35 with zaprinast will be performed in cardiac, renal and inflammatory cells in the absence and presence of selective GPR 35 antagonists to determine the effect on downstream signalling as well as potential effects on collagen synthesis and cytokine expression levels.

This project is suited for an Honours/Masters research project.