"Glycoprotein involvement in cardiac fibrobiast-myocyte communication "
“糖蛋白参与心脏成纤维细胞-肌细胞通讯”
基本信息
- 批准号:8183670
- 负责人:
- 金额:$ 32.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-07-01 至 2018-05-31
- 项目状态:已结题
- 来源:
- 关键词:Acute myocardial infarctionAmino AcidsAngioplastyApoptosisArchitectureBiological MarkersBlood CirculationBlood flowCardiacCardiac MyocytesCardiovascular DiseasesCell CommunicationCell DeathCell surfaceCellsCessation of lifeCicatrixClinicalCoculture TechniquesCommunicationComplementComplexCoronary arteryDetectionDevelopmentDiagnosisEnsureEnvironmentExtracellular MatrixFarGoFibroblastsGlycoconjugatesGlycoproteinsGoldHeartHeart failureHydrogen PeroxideHypoxiaImmunohistochemistryInfarctionInjuryInstructionIschemiaKnowledgeLabelLeadLinkMass Spectrum AnalysisMethodsMonitorMuscleMuscle CellsMyocardialMyocardial InfarctionMyocardial IschemiaMyocardiumMyofibroblastNecrosisOligosaccharidesOxidative StressPatientsPeptidesPhenotypePlayPolysaccharidesPredispositionPrincipal InvestigatorProteinsProteomeProteomicsReactionRegulationRelative (related person)Reperfusion TherapyRiskRoleSamplingSerumSignal TransductionSiteSliceSpecificityStressTechnologyTherapeutic InterventionTissuesTranslatingTroponinValidationVentricular RemodelingWound Healingautocrinebasecell typeclinical Diagnosisclinically relevantglycosylationin vivoinjuredinnovationmultiple reaction monitoringnovelparacrineresponseresponse to injury
项目摘要
The blockage of coronary arteries can result in a heart attack (acute myocardial infarction; Ml) and
permanent loss of cardiac muscle tissue. The resulting destruction of the complex cardiac architecture,
formation of scar tissue, and myocardial remodeling increases risk of death. The heart's initial response to
injury is synchronous and involves, in part, the reciprocal interaction between cardiac fibroblasts and
myocytes, the two primary cell types comprising the heart. Recent findings suggest that soluble proteins
secreted from cardiac fibroblasts and myocytes, also called the secretome, can modulate the infarct
microenvironment (extracellular matrix, ECM). It is the cell surface that not only acts as a physical barrier
but senses of the local ECM microenvironment that initiates the intrinsic cellular protective mechanisms upon
injury. Thus, the cell-environment interface is the main site of this interplay. We hypothesize that
fibroblasts are the linchpin and their respond to injury launches wound healing while also promoting myocyte
survival. Fibroblasts accomplish this by altering the ECM microenvironment surrounding myocytes,
especially those present in the infarct border zone. Many of the proteins comprising cell-environment
interface are glycosylated. In this proposal, we will use a number of innovative methods to target, enrich,
quantify (relative and absolute) and characterize the glycoproteome of the cell-environment interface of
myocytes and fibroblasts alone and in co-culture with and without injury induced by H2O2. This includes using
a novel twist when co-culturing, in which the proteins from one cell type have a covalent quantitative labeled
which provides a mass spectrometry friendly marker to distinguishing the cell origin of each protein. We
hypothesize that cell-specific glycoproteome comprising the cell-environment interface is responsible to the
intrinsic susceptibility to H2O2 of myocytes compared to fibroblasts (SA 1). Furthermore, that a subset of the
fibroblast-specific secreted proteins which are elevated in co-culture induces myocyte-protection and this
protective phenotype is enhanced by the action of when fibroblast, themselves are injured (SA-2). Finally,
we hypothesize that glycoproteins present in the microenvironment which are exclusively elevated in
response of H2O2 will be detected in the circulation of patients with myocardial injury (ischemia) prior to the
elevation of cardiac troponins (gold standard markers for Ml). In summary, the protein complement of the
cell-environment interface has not been fully elucidated for either cardiac fibroblasts or myocytes. This
knowledge is fundamental to developing clinical approaches to protect the heart and potentially provide
robust clinical biomarkers
RELEVANCE (See instructions);
This is the first systematic analysis of the glycoproteins which comprise the secretome and cell surface of
myocytes and fibroblast, two major cell types of the heart, for which their interaction is synergetic and can
results in myocyte protection. These protective glycoproteins could be targets suitable for therapeutic
intervention. As well, the myocardial and cardiac fibroblast specific hypoxic stimulated secreted proteins
from cardiac fibroblasts and myocytes that circulating and are elevated in patients with myocardial ischemia
冠状动脉阻塞可导致心脏病发作(急性心肌梗死;Ml)
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(4)
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Jennifer E Van Eyk其他文献
Transgenic Model of Myofilament Dysfunction in Myocardial Stunning
心肌顿抑中心肌肌丝功能障碍的转基因模型
- DOI:
10.1203/00006450-199904020-00171 - 发表时间:
1999-04-01 - 期刊:
- 影响因子:3.100
- 作者:
Anne M Murphy;Dimitrios Georgakopoulos;David A Kass;Jennifer E Van Eyk;Eduardo Marban - 通讯作者:
Eduardo Marban
Jennifer E Van Eyk的其他文献
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{{ truncateString('Jennifer E Van Eyk', 18)}}的其他基金
CORALE-SeroNet Immune Bioanalytics Core
CORALE-SeroNet 免疫生物分析核心
- 批准号:
10688398 - 财政年份:2020
- 资助金额:
$ 32.8万 - 项目类别:
CORALE-SeroNet Immune Bioanalytics Core
CORALE-SeroNet 免疫生物分析核心
- 批准号:
10222435 - 财政年份:2020
- 资助金额:
$ 32.8万 - 项目类别:
A new post-translational modification, citrullination, changes in heart failure
一种新的翻译后修饰,瓜氨酸化,心力衰竭的变化
- 批准号:
8256288 - 财政年份:2012
- 资助金额:
$ 32.8万 - 项目类别:
A new post-translational modification, citrullination, changes in heart failure
一种新的翻译后修饰,瓜氨酸化,心力衰竭的变化
- 批准号:
8431700 - 财政年份:2012
- 资助金额:
$ 32.8万 - 项目类别:
TAS::75 0872::TAS THE JOHNS HOPKINS PROTEOMIC INNOVATION CENTER IN HEART FAILURE
塔斯马尼亚州::75 0872::塔斯马尼亚州约翰霍普金斯大学心力衰竭蛋白质组学创新中心
- 批准号:
8320842 - 财政年份:2010
- 资助金额:
$ 32.8万 - 项目类别:
CRT and Mitochondrial Function and Proteome Post-Translational Modifications
CRT 与线粒体功能和蛋白质组翻译后修饰
- 批准号:
8011127 - 财政年份:2010
- 资助金额:
$ 32.8万 - 项目类别:
TAS::75 0872::TAS THE JOHNS HOPKINS PROTEOMIC INNOVATION CENTER IN HEART FAILURE
塔斯马尼亚州::75 0872::塔斯马尼亚州约翰霍普金斯大学心力衰竭蛋白质组学创新中心
- 批准号:
8537322 - 财政年份:2010
- 资助金额:
$ 32.8万 - 项目类别:
TAS::75 0872::TAS THE JOHNS HOPKINS PROTEOMIC INNOVATION CENTER IN HEART FAILURE
塔斯马尼亚州::75 0872::塔斯马尼亚州约翰霍普金斯大学心力衰竭蛋白质组学创新中心
- 批准号:
8175610 - 财政年份:2010
- 资助金额:
$ 32.8万 - 项目类别:
TAS::75 0872::TAS THE JOHNS HOPKINS PROTEOMIC INNOVATION CENTER IN HEART FAILURE
塔斯马尼亚州::75 0872::塔斯马尼亚州约翰霍普金斯大学心力衰竭蛋白质组学创新中心
- 批准号:
8727408 - 财政年份:2010
- 资助金额:
$ 32.8万 - 项目类别:
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