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.

Public Health Relevance

Cardiovascular diseases continue to be a leading cause of death and disability. Despite this alarming fact, there is lack of effectual treatment and the molecular mechanisms that regulate these devastating diseases remain elusive. Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure and volume overload in the heart often leads to cardiac hypertrophy, an increase in the size of heart and cardiomyocytes. Progression of cardiac hypertrophy and adverse cardiac remodeling often lead to dilated cardiomyopathy (DCM), which displays weakened and enlarged heart and decreased heart function. DCM is the precursor of the end-staged systolic heart failure (HF), which is the leading cause of death in the U.S. The overall goal of our investigation proposed here is to uncover the regulatory circuits in cardiac hypertrophy and dilated cardiomyopathy. This study will provide important insights into our understanding of the molecular events underlying cardiac function and cardiomyopathy. The molecular mechanisms revealed in these studies may apply to pathophysiologically-related cardiac conditions such as human congenital heart defect, hypertrophy, dilated cardiomyopathy and cardiac failure. These studies are an important prerequisite to developing therapeutic strategies that ultimately limit the progression of DCM to HF.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiac Contractility, Hypertrophy, and Failure Study Section (CCHF)
Program Officer
Sopko, George
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Children's Hospital Boston
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