Molecular mechanisms of dilated cardiomyopathy

描述(申请人提供)：心血管疾病仍然是世界范围内导致死亡和残疾的主要原因。肥厚型心肌病(HCM)、扩张型心肌病(DCM)通常进展为收缩性心力衰竭(HF)，是美国人的主要死亡原因。然而，这些心血管疾病的分子机制尚不完全清楚。我们鉴定了CIP是一种新的心脏特异性核蛋白，并证明了CIP调节心肌细胞肥大和扩张型心肌病。我们研究的总体目标是揭示CIP在心脏和心脏疾病中的生理和病理功能。具体目标为：具体目标1.确定CIP在心脏中的体内功能。具体目标#2.检验CIP预防肥厚性心肌病进展为扩张型心肌病和心力衰竭的假说。具体目的#3.明确CIP调节HCM和DCM的分子机制。这项研究将为我们理解心脏功能和心肌病背后的分子事件提供重要的见解，并是制定纠正或绕过心血管疾病的治疗策略的重要前提。

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.