Adhesion Molecules of the Intercalated Disc in Cardiomyopathy

心肌病闰盘的粘附分子

• 批准号: 7905098
• 负责人: Kirk U Knowlton
• 金额: $ 31.07万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7905098
• 关键词: Actins; Adherens Junction; Adhesives; Adult; Affect; Alleles; Arrhythmia; Arrhythmogenic Right Ventricular Dysplasia; Attention; Binding; Binding Proteins; Breeding; Cardiac; Cardiac Myocytes; Cardiomyopathies; Cardiovascular system; Cell Adhesion Molecules; Cell membrane; Cell-Cell Adhesion; Cell-Matrix Junction; Cells; Complex; Connexin 43; Coupling; Coxsackie Viruses; Cytoskeleton; Data; Desmosomes; Development; Dilated Cardiomyopathy; Dysphasia; Embryo; Embryonic Heart; Epithelial Cells; Extracellular Matrix; Fascia; Fascia adherens; Gap Junctions; Genetic Recombination; Growth; Heart; Heart Diseases; Heart Hypertrophy; Heart failure; Human; Hypertrophy; Immunoglobulin Domain; Inherited; Integral Membrane Protein; Intercalated disc; Intercellular Junctions; Investigation; Knock-out; Knockout Mice; Laboratories; Lead; Learning; Link; Location; Mechanics; Mediating; Membrane; Microfilaments; Molecular; Mus; Muscle Cells; Myocardium; Myosin Heavy Chains; N-Cadherin; Pathogenesis; Pathway interactions; Pattern; Physiologic intraventricular pressure; Property; Protein Array; Protein Binding; Proteins; Reporting; Role; Sarcolemma; Side; Structure; Technology; Text; Tight Junctions; Time; Tissues; Transgenic Mice; Transgenic Organisms; Troponin I; Ventricular; Ventricular Function; adenovirus receptor; base; cardiogenesis; cell type; mortality; normal aging; numb protein; pressure; programs; promoter; protein structure; receptor binding; receptor expression; transgene expression; ventricular hypertrophy

ntercalated discs (ICD) are the major cardiac cell-cell adhesion structures, which connect muscle cells to one another. They consist of an array of proteins, which are categorized into three major junctional complexes, fascia adherens junctions, desmosomes, and gap junctions, and are essential for maintaining mechanical and electrical coupling between neighboring muscle cells/Abnormalities in the intercalated disc have been linked to hereditary forms of dilated cardiomyopathy such as arrhythmogenic right ventricular dysphasia/ cardiomyopathy (ARVD/C). Also abnormalities in the intercalated disc has been reported in the setting of cardiomyopathy. The coxsackievirus adenovirus receptor (CAR) is localized primarily at the ntercalated disc in the adult heart. While we and others have shown that CAR expression is required for normal cardiovascular development, relatively little is known of the functional significance of CAR and its associated molecules in the adult heart and in formation of the normal intercalated disc. The underlying hypothesis for this project is that CAR and ZO-1 expression are required for normal cardiac function in the adult heart and with pressure overload and that the absence of these molecules will lead to abnormal cardiac function that will be associated with abnormalities in intercalated .disc structure and function. Specific Aims: Aim 1: Determine the effect of cardiac specific and inducible CAR knockout on ventricular function in the adult heart during normal growth and with pressure overload. Aim 2: Determine the molecular and cellular mechanisms by which CAR disruption affects cardiac function with an emphasis on adjacent transmembrane proteins and sarcolemmal proteins that are located on the cytoplasmic side of the membrane within the intercalated disc. Specific Aim 3: Determine whether cardiac myocyte expression of ZO-1 is required for formation of the normal embryonic heart and its role in normal cardiac function and intercalated disc formation in the adult heart.

间插椎间盘（intercalated disc， ICD）是主要的心脏细胞-细胞黏附结构，它连接肌肉细胞和血管