Erasmus MC : Project number 2

The hypertrophic remodeling of the heart that occurs after a myocardial infarction in surviving tissue seems an appropriate response aimed at restoring normal pump function. Unlike the LV hypertrophy in response to exercise-training, however, post-MI remodeling constitutes an independent risk factor for the development of heart failure later on. The molecular pathways underlying post-MI remodeling and progression towards heart failure remain incompletely understood. We propose that the propensity to develop heart failure originates from gene reprogramming events early after infarction. By applying global ‘–omics’ techniques we aim to identify the transcription factors that mediate the genetic reprogramming involved in LV hypertrophic remodeling, but that differ between post-MI versus exercise-training. As animal model we use the pig, which cardiac physiology is similar to human. We collect data on changes in the transcriptome and the nuclear proteome early after MI or exercise-training, and analyse these date for common transcription factor binding motifs and differentially expressed transcription factors. By this integrative approach, we hope to identify novel targets for therapy that will prevent progression towards heart failure.