Adhesion Molecules of the Intercalated Disc in Cardiomyopathy
心肌病闰盘的粘附分子
基本信息
- 批准号:7905098
- 负责人:
- 金额:$ 31.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:ActinsAdherens JunctionAdhesivesAdultAffectAllelesArrhythmiaArrhythmogenic Right Ventricular DysplasiaAttentionBindingBinding ProteinsBreedingCardiacCardiac MyocytesCardiomyopathiesCardiovascular systemCell Adhesion MoleculesCell membraneCell-Cell AdhesionCell-Matrix JunctionCellsComplexConnexin 43CouplingCoxsackie VirusesCytoskeletonDataDesmosomesDevelopmentDilated CardiomyopathyDysphasiaEmbryoEmbryonic HeartEpithelial CellsExtracellular MatrixFasciaFascia adherensGap JunctionsGenetic RecombinationGrowthHeartHeart DiseasesHeart HypertrophyHeart failureHumanHypertrophyImmunoglobulin DomainInheritedIntegral Membrane ProteinIntercalated discIntercellular JunctionsInvestigationKnock-outKnockout MiceLaboratoriesLeadLearningLinkLocationMechanicsMediatingMembraneMicrofilamentsMolecularMusMuscle CellsMyocardiumMyosin Heavy ChainsN-CadherinPathogenesisPathway interactionsPatternPhysiologic intraventricular pressurePropertyProtein ArrayProtein BindingProteinsReportingRoleSarcolemmaSideStructureTechnologyTextTight JunctionsTimeTissuesTransgenic MiceTransgenic OrganismsTroponin IVentricularVentricular Functionadenovirus receptorbasecardiogenesiscell typemortalitynormal agingnumb proteinpressureprogramspromoterprotein structurereceptor bindingreceptor expressiontransgene expressionventricular hypertrophy
项目摘要
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.
间盘(ICD)是主要的心肌细胞-细胞粘附结构,其将肌细胞连接到
彼此它们由一系列蛋白质组成,这些蛋白质被分为三个主要的连接蛋白。
复合体、粘连筋膜连接、桥粒和缝隙连接,并且对于维持
相邻肌细胞之间的机械和电耦合/椎间盘中的椎间盘突出
与遗传性扩张型心肌病有关,
语言障碍/心肌病(ARVD/C)。在文献中也报道了闰盘的异常。
心肌病的背景。柯萨奇病毒腺病毒受体(CAR)主要定位于
在成人心脏的椎间盘。虽然我们和其他人已经证明CAR表达是
尽管CAR在正常的心血管发育中起重要作用,但对CAR及其功能的意义知之甚少。
相关分子在成人心脏和正常闰盘的形成。底层
该项目的假设是CAR和ZO-1表达是正常心脏功能所必需的。
成年人的心脏和压力超负荷,缺乏这些分子会导致心脏异常
与闰盘结构和功能异常相关的功能。
具体目标:
目的1:确定心脏特异性和诱导性CAR敲除对心肌梗死患者心室功能的影响。
正常生长和压力超负荷的成年心脏。
目的2:确定CAR破坏影响心脏功能的分子和细胞机制
重点是位于细胞膜上的相邻跨膜蛋白和肌膜蛋白。
在闰盘内的膜的细胞质侧。
具体目标3:确定心肌细胞ZO-1的表达是否是形成心肌细胞凋亡所必需的。
正常胚胎心脏及其在成人心脏功能和闰盘形成中的作用
心
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kirk U Knowlton其他文献
Cardiac-specific deletion of SOCS3 improved lipopolysaccharid e-induced cardiac dysfunction via mitochondria stabilization
心脏特异性删除 SOCS3 通过线粒体稳定改善脂多糖诱导的心脏功能障碍
- DOI:
- 发表时间:
2009 - 期刊:
- 影响因子:0
- 作者:
Futamata N;Yasukawa H;Oba T;Mawatari K;Nagata T;Kyogoku S;Hoshijima M;Kirk U Knowlton;Imaizumi T - 通讯作者:
Imaizumi T
LP(A) MEASUREMENT IN PRIMARY PREVENTION POPULATION MAY LEAD TO INCREASED UTILIZATION OF STATIN THERAPY, A REAL-WORLD EXPERIENCE
初级预防人群中 LP(A) 测量可能导致他汀类药物治疗的利用率增加,这是一个真实世界的经验
- DOI:
10.1016/j.ajpc.2023.100556 - 发表时间:
2023-09-01 - 期刊:
- 影响因子:5.900
- 作者:
Viet T Le;Heidi T May;Jeffrey L. Anderson;Tami Bair;Stacey Knight;Benjamin D. Horne;Kirk U Knowlton - 通讯作者:
Kirk U Knowlton
Prevention of Myocardial Ischemia-Reperfusion Injury in Cardiac-Specific SOCS3 Knockout Mice by enhanced activation of vardioprotective signaling pathways
通过增强心脏保护信号通路的激活来预防心脏特异性 SOCS3 敲除小鼠的心肌缺血再灌注损伤
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:0
- 作者:
T nagata;H Yasukawa;T Oba;S Pradervand;K mawatari;S Kyogoku;H Ohshima;T Minami;K Sasaki;T Yajima;M Hoshijima;Kirk U Knowlton;T Imaizumi;Y Fukumoto - 通讯作者:
Y Fukumoto
The Role of Suppressor of Cytokine Signaling-3 in Lipopolysa ccharide-induced Left Ventricular Dysfunction in Mice
细胞因子信号转导3抑制剂在脂多糖诱导的小鼠左心室功能障碍中的作用
- DOI:
- 发表时间:
2010 - 期刊:
- 影响因子:0
- 作者:
Futamata N;Yasukawa H;Oba T;Mawatari K;Kirk U Knowlton;Imaizumi T - 通讯作者:
Imaizumi T
Variants at the Interleukin 1 Gene Locus and Pericarditis.
白细胞介素 1 基因座的变异与心包炎。
- DOI:
10.1001/jamacardio.2023.4820 - 发表时间:
2023 - 期刊:
- 影响因子:24
- 作者:
Rosa B. Thorolfsdottir;Andrea B Jonsdottir;Gardar Sveinbjornsson;Hildur M Aegisdottir;A. Oddsson;Olafur A. Stefansson;G. Halldorsson;S. Saevarsdottir;G. Thorleifsson;L. Stefánsdóttir;O. B. Pedersen;E. Sørensen;J. Ghouse;A. Raja;Chaoqun Zheng;Elvira Silajdzija;S. A. Rand;C. Erikstrup;H. Ullum;Christina Mikkelsen;K. Banasik;S. Brunak;Erna V. Ivarsdottir;A. Sigurdsson;Doruk Beyter;Árni Sturluson;Hafsteinn Einarsson;V. Tragante;H. Helgason;S. Lund;B. Halldórsson;Brynja D. Sigurpálsdóttir;I. Olafsson;D. Arnar;G. Thorgeirsson;Kirk U Knowlton;Lincoln D Nadauld;S. Gretarsdottir;A. Helgadóttir;S. Ostrowski;Daniel F Gudbjartssson;I. Jónsdóttir;H. Bundgaard;H. Hólm;P. Sulem;Kári Stefánsson - 通讯作者:
Kári Stefánsson
Kirk U Knowlton的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kirk U Knowlton', 18)}}的其他基金
Adhesion Molecules of the Intercalated Disc in Cardiomyopathy
心肌病闰盘的粘附分子
- 批准号:
7331346 - 财政年份:2007
- 资助金额:
$ 31.07万 - 项目类别:
Biomechanical Stress Pathways and Cardiomyopathy
生物力学应激途径和心肌病
- 批准号:
7288521 - 财政年份:2005
- 资助金额:
$ 31.07万 - 项目类别:
Role of mTOR, a Component of the Akt Pathway, in Regulating Cardiac Function
mTOR(Akt 通路的一个组成部分)在调节心脏功能中的作用
- 批准号:
8386980 - 财政年份:2005
- 资助金额:
$ 31.07万 - 项目类别:
CORE--MYOCARDIAL CELL BIOLOGY AND VIRAL VECTOR FACILITY
核心——心肌细胞生物学和病毒载体设施
- 批准号:
7098691 - 财政年份:2005
- 资助金额:
$ 31.07万 - 项目类别:
Dystrophin-glyoprotein complex and dilated cardiomyopathy
肌营养不良蛋白-糖蛋白复合物与扩张型心肌病
- 批准号:
6564971 - 财政年份:2002
- 资助金额:
$ 31.07万 - 项目类别:
CORE--CELL BIOLOGY AND VIRAL VECTOR FACILITY
核心--细胞生物学和病毒载体设施
- 批准号:
6651374 - 财政年份:2002
- 资助金额:
$ 31.07万 - 项目类别:
Dystrophin-glycoprotein complex in viral cardiomyopathy
病毒性心肌病中的肌营养不良蛋白-糖蛋白复合物
- 批准号:
6382595 - 财政年份:2001
- 资助金额:
$ 31.07万 - 项目类别:
Dystrophin-glycoprotein complex in viral cardiomyopathy
病毒性心肌病中的肌营养不良蛋白-糖蛋白复合物
- 批准号:
6755170 - 财政年份:2001
- 资助金额:
$ 31.07万 - 项目类别:
相似海外基金
Oral pathogen - mediated pro-tumorigenic transformation through disruption of an Adherens Junction - associated RNAi machinery
通过破坏粘附连接相关的 RNAi 机制,口腔病原体介导促肿瘤转化
- 批准号:
10752248 - 财政年份:2024
- 资助金额:
$ 31.07万 - 项目类别:
Adherens junction dynamics and function in epithelial tissue morphogenesis
粘附连接动力学和上皮组织形态发生中的功能
- 批准号:
469118 - 财政年份:2022
- 资助金额:
$ 31.07万 - 项目类别:
Operating Grants
Adherens Junction dysfunction in Hidradenitis Suppurativa
化脓性汗腺炎的粘附连接功能障碍
- 批准号:
10701323 - 财政年份:2022
- 资助金额:
$ 31.07万 - 项目类别:
Adherens junction proteins in neuron-glia interactions
神经元-胶质细胞相互作用中的粘附连接蛋白
- 批准号:
9978138 - 财政年份:2019
- 资助金额:
$ 31.07万 - 项目类别:
Elucidation of the function of Focal adherens junction in morphogenesis
阐明焦点粘附连接在形态发生中的功能
- 批准号:
19K16145 - 财政年份:2019
- 资助金额:
$ 31.07万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Identifying and characterizing the effect of Aip1 on adherens junction remodeling in Drosophila follicular epithelium
鉴定和表征 Aip1 对果蝇滤泡上皮粘附连接重塑的影响
- 批准号:
528450-2018 - 财政年份:2018
- 资助金额:
$ 31.07万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Master's
Src-mediated pathways regulating adherens junction assembly.
Src 介导的途径调节粘附连接组装。
- 批准号:
10166863 - 财政年份:2017
- 资助金额:
$ 31.07万 - 项目类别:
Src-mediated pathways regulating adherens junction assembly.
Src 介导的途径调节粘附连接组装。
- 批准号:
9310733 - 财政年份:2017
- 资助金额:
$ 31.07万 - 项目类别:
The function and interaction of focal adhesion and adherens junction in bone mechanosensing and mechanotransduction.
粘着斑和粘附连接在骨力传感和力转导中的功能和相互作用。
- 批准号:
17K17307 - 财政年份:2017
- 资助金额:
$ 31.07万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
a-catenin and its binding partners in adherens junction assembly and function
α-连环蛋白及其在粘附连接组装和功能中的结合伙伴
- 批准号:
357714 - 财政年份:2016
- 资助金额:
$ 31.07万 - 项目类别:
Operating Grants