ROLE OF CMYBP-C IN THE REGULATION OF MYOCARDIUM

CMYBP-C 在心肌调节中的作用

• 批准号: 7722750
• 负责人: Richard L Moss
• 金额: $ 5.06万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722750
• 关键词: Affect; American; Cardiac; Cardiac Myocytes; Cardiac Myosins; Charge; Computer Retrieval of Information on Scientific Projects Database; Contracts; Development; Disease; Drug Controls; Familial Hypertrophic Cardiomyopathy; Funding; Genes; Genetically Engineered Mouse; Grant; Growth; Health; Heart; Heart failure; Hereditary Disease; Institution; Laboratories; Lead; Left; Location; Molecular; Molecular Conformation; Molecular Structure; Mus; Muscle Cells; Mutation; Myocardial Contraction; Myocardium; Patients; Protein Conformation; Proteins; Regulation; Research; Research Personnel; Resources; Role; Source; Speed; Thick; United States National Institutes of Health; Ventricular; X ray diffraction analysis; X-Ray Diffraction; beamline; gene therapy; mortality; myosin-binding protein C

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Familial hypertrophic cardiomyopathy (FHC) caused by mutation in the gene encoding cardiac myosin binding protein-C (cMyBP-C) is estimated to affect one in 1,500 Americans. This genetic disorder of the heart is characterized by increased growth in thickness of the left ventricular wall. Despite over 30 years of research, the exact structural location and function of cMyBP-C in muscle cells is far from clear. Our research investigates the structural changes in hearts from genetically-engineered mice which lack cMyBP-C or have cMyBP-C that has been altered to mimic this protein's conformation as it changes in health and disease. We believe cMyBP-C acts to "put the breaks" on the speed of the contracting cycle in heart muscle cells. Using the approach of X-ray diffraction (on the BioCAT beamline, Argonne National Laboratory), we will probe for changes in the molecular structure of heart muscle cells that arise from removing or altering cMyBP-C in our genetically-engineered mice. In support of our hypothesis, we have already found profound effects on the molecular structure in mice lacking this protein. Additionally, altering the conformation of cMyBP-C affects cardiac function, which may be due to changes in its molecular "charge". We will therefore examine structural changes arising from changing the charge on cMyBP-C. Despite advances in biomedicine, the 5-year mortality of heart failure patients remains well above 50%. Thus, understanding the role of cMyBP-C in governing contraction of the heart can lead to development of new treatments such as gene therapy and drugs that control the conformation of cMyBP-C.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 据估计，由编码心脏肌球蛋白结合蛋白-C（CMYBP-C）突变引起的家族性肥厚性心肌病（FHC）估计会影响1,500名美国人中的一个。 这种心脏的遗传疾病的特征是左心室壁厚度的生长增加。 尽管进行了30多年的研究，但CMYBP-C在肌肉细胞中的确切结构位置和功能远非清晰。 我们的研究调查了缺乏CMYBP-C或具有CMYBP-C的遗传学工程小鼠的心脏结构变化，该cmybp-c已改变以模仿该蛋白质的构素，因为它在健康和疾病上的变化都会改变。 我们认为，CMYBP-C的作用是“将休息时间”在心肌细胞中的收缩循环速度上。 使用X射线衍射的方法（在BioCat光束线上，Argonne National Laboratory上），我们将探测由遗传工程小鼠中去除或改变CMYBP-C引起的心脏肌肉细胞的分子结构的变化。 为了支持我们的假设，我们已经发现了缺乏该蛋白质的小鼠的分子结构的深远影响。 另外，改变CMYBP-C的构象会影响心脏功能，这可能是由于其分子“电荷”的变化所致。 因此，我们将检查因更改CMYBP-C上的电荷而产生的结构变化。 尽管生物医学取得了进步，但心力衰竭患者的5年死亡率仍远高于50％。 因此，了解CMYBP-C在控制心脏收缩中的作用可以导致发展新疗法的发展，例如基因疗法和控制CMYBP-C构象的药物。