Characterization of GPR35 in models of cardiac and renal disease

Summary 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. 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. This project will assess the expression of GPR 35 in archived tissues from various animal models of cardiac disease, including myocardial infarction, pressure-overload hypertrophy and diabetes using immunohistochemistry and real time PCR.

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. This project will assess the expression of GPR 35 in archived tissues from various animal models of cardiac disease, including myocardial infarction, pressure-overload hypertrophy and diabetes using immunohistochemistry and real time PCR. Under hypoxic conditions, known to increase GPR35, cell culture experiments utilising cardiac cells will be performed in the absence and presence of selective GPR 35 antagonists to determine the effect on GPR 35 gene expression, as well as determine effects on collagen synthesis and hypertrophy using proline and leucine incorporation assays respectively.