Inherited myosin mutations that cause heart disease

遗传性肌球蛋白突变导致心脏病

基本信息

批准号：
7057494
负责人：
TODD Joseph HERRON
金额：
$ 4.45万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7057494
关键词：
calcium binding protein calcium flux cardiac myocytes enzyme structure gene mutation genetic disorder heart contraction hypertrophic myocardiopathy laboratory rat molecular pathology myocardium disorder myosins pathologic process postdoctoral investigator protein structure function

项目摘要

DESCRIPTION (provided by applicant): In cases of inherited cardiomyopathy, the heart muscle thickens or dilates in the absence of obvious disease conditions (such as hypertension). Recent research into the causes of inherited hypertrophic and dilated cardiomyopathy has shown that inherited single-gene mutations of cardiac sarcomere proteins (proteins that are responsible for heart muscle contraction) may cause disease. The most commonly affected sarcomere protein is myosin heavy chain. Myosin heavy chain is the heart's molecular motor and mutations of myosin have been identified to cause hypertrophic (HCM) and dilated (DCM) cardiomyopathy. Each type of familial cardiomyopathy is characterized by distinct functional changes. The study of single-gene mutations that trigger heart disease by distinct functional impairments provides a unique opportunity for defining important molecules involved in disease progression. Results obtained here will examine how clinically relevant myosin mutations cause HCM or DCM and provide insight into mechanisms of heart disease. Although these monogenic inherited disorders account for a small fraction of total heart failure cases, study of cellular responses to such gene mutations are also likely to be relevant to more common forms of heart failure.

描述（由申请人提供）：在遗传性心肌病的情况下，在没有明显的疾病疾病（例如高血压）的情况下，心肌会增厚或扩张。最近对遗传性肥厚和扩张性心肌病的原因的研究表明，遗传性心肌蛋白的单基因突变（导致心脏肌肉收缩的蛋白质）可能会导致疾病。最常见的肌动蛋白是肌球蛋白重链。肌球蛋白重链是心脏的分子运动，已经确定肌球蛋白的突变会引起肥厚（HCM）和扩张（DCM）心肌病。每种类型的家族性心肌病的特征都具有明显的功能变化。通过不同的功能障碍引发心脏病的单基因突变的研究为定义参与疾病进展的重要分子提供了独特的机会。此处获得的结果将检查临床上相关的肌球蛋白突变如何引起HCM或DCM，并提供对心脏病机理的见解。尽管这些单基因遗传性疾病占了总心力衰竭病例的一小部分，但对这种基因突变的细胞反应的研究也可能与更常见的心力衰竭形式有关。