I propose to investigate the relevance of arginine methylation of cardiac troponin I (ArgMe-cTnI), which is a novel cTnI post-translational modification reported here for the first time, in aetiology and diagnosis of cardiac disease. My hypothesis is that cardiac disease, including cardiomyopathies, is associated with changes in ArgMe-cTnI levels. My objectives are: 1) to demonstrate lower levels of ArgMe-cTnI in human cardiac samples from patients with hypertrophic cardiomyopathy, compared to controls (samples from Papworth Hospital) and 2) to measure the levels of ArgMe-cTnI in the blood of patients with acute myocardial infarction (who, by definition, have elevated cTnI in circulation).
Objective 1 will determine whether low levels of ArgMe-cTnI can be a biomarker for hypertrophic and diabetic cardiomyopathies, which may enable detection of early disease. Objective 2 will allow investigation of the potential of ArgMe-cTnI to be a more robust and specific biomarker of myocardial infarction than current cTnI assays. This project is focused on translating promising preliminary data into the clinical arena.