Uncovering conserved mechanisms of cardiac fibrosis using Drosophila
The overall goal of this project is to develop and validate the Drosophila system as a model for understanding the mechanisms of cardiac fibrosis. Fibrosis in the mammalian heart is the result of an inflammatory response to aging and cardiac injury such as myocardial infarction, and results in a poorly functioning heart leading to morbidity and death. We present preliminary data demonstrating that the Drosophila heart undergoes age-dependent fibrosis, that correlates with age-dependent cardiac decline. In addition, in mutants affecting a cardiac-restricted gene we detect premature fibrosis. These findings suggest that Drosophila may be useful as a genetic model to define the mechanisms of cardiac fibrosis. To generate supportive data critical for initial publications and grant submissions, we will firstly define the timecourse of cardiac fibrosis in control and mutant lines, to correlate changes in heart function with the onset of fibrosis. Secondly, we will identify the components of the fibrotic material, and analyze the transcriptional regulation of a signature component of the fibrotic material.