Molecular Imaging of Collagen in Cardiac Remodelling

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Remodeling of collagen plays a crucial role in the pathogenesis of several diseases including heartfailure, atherosclerosis, aortic aneurysm dissection, lung and liver fibrosis. The Aim of this project is toinvestigate the role of collagen deposition (fibrosis) on left ventricular (LV) remodeling and cardiacfunction post myocardial infarction (MI) and the potential impact of therapies that aim at modulating thefibrotic response. The project will utilize a commercially available collagen I-binding MR contrast agent and an established murine model of post-MI remodeling. In parallel, we will develop and evaluate peptides that selectively bind to collagen types I or III and which allow discrimination between the different types of collagen and thus enhance our understanding of collagen turnover in disease progression. The probes can be labelled with radioisotopes for initial screening tool in biological studies using PET/SPECT imaging. The most promising probe can then be labelled with gadolinium for MRI experiments. All in vivo imaging experiments would be complemented by ex vivo analysis. BACKGROUND: Cardiovascular diseases (CVD) including coronary heart disease, stroke, heart failure (HF), cardiomyopathy, and atrial fibrillation affect more that 2.3 million people and account for ~27% of all deaths in the UK. Amongst all CVD, myocardial infarction (MI) and heart failure are the most frequent with ~175,000 people experiencing episodes of acute MI per year and more than 500,000 people are living with HF in the UK.