Anti-fibrotic and/or anti-inflammatory compound/s for the treatment of heart failure

The pathophysiologic progression to heart failure is a complex process. Initial insults such a myocardial infarction or chronic hypertension, trigger the activation of neurohormonal systems in the body in an attempt to restore cardiac function. However, long-term activation of this system becomes maladaptive by causing cellular and molecular changes in the heart which leads to cardiac remodelling and eventually leading to heart failure. Cardiac fibrosis is one of the key cardiac remodelling processes. Over recent years, epidemiologic, clinical and experimental data have accumulated to suggest that inflammation is a critical contributor to the pathogenesis of heart failure, being a key driver of fibrosis. Inflammation is likely stimulated by accompanying metabolic factors such as obesity. Together with other drivers resultant cardiovascular remodelling leads to the well characterized heart failure phenotype. Thus, anti-fibrotic and anti-inflammatory therapy could be of particular important in the management of heart failure. We have recently validated novel pathways that are particularly important for cardiac fibrosis. In collaboration with Monash Institute of Pharmaceutical Sciences (MIPS), we have developed novel compounds that inhibit the fibrotic pathway with anti-fibrotic and/or anti-inflammatory activity. This project is to investigate an orally administered novel anti-fibrotic and/or anti-inflammatory compound/s for the treatment of cardiovascular disease including heart failure using suitable animal models established in our group. This study will test the ability of the compound/s to both prevent and to reverse myocardial fibrosis and inflammation associated with the heart failure phenotype. It is anticipated that this study will involve the use of animal models in mice, cardiac function measurement with echocardiography and pressure-volume relationship analysis, Western blotting, immunohistochemistry, gene expression analysis with PCR.