Molecular mechanisms of dilated cardiomyopathy

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DESCRIPTION (provided by applicant): Cardiovascular diseases continue to be a leading cause of death and disability world- wide. Hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) often progress to systolic heart failure (HF), the leading cause of death in the U.S. However, the molecular mechanisms underlying these cardiovascular disorders are not fully understood. We identified CIP as a novel cardiac-specific nuclear protein and demonstrated that CIP modulates cardiomyocyte hypertrophy and dilated cardiomyopathy. The overall goal of our study is to uncover the physiological and pathological functions of CIP in the heart and heart diseases. The specific aims are: Specific Aim #1. To determine the in vivo function of CIP in the heart. Specific Aim #2. To test the hypothesis that CIP prevents the progression of HCM to DCM and heart failure. Specific Aim #3. To define the molecular mechanism by which CIP regulates HCM and DCM. This study will provide important insights into our understanding the molecular events underlying cardiac function and cardiomyopathy and are an important prerequisite to developing therapeutic strategies that correct or circumvent cardiovascular diseases.