MicroRNA as mediators of angiogenesis & ischemic myocardial repair
MicroRNA 作为血管生成的介质
基本信息
- 批准号:8837681
- 负责人:
- 金额:$ 49.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-12 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAreaBone MarrowCardiacCardiac MyocytesCell SurvivalCell TherapyCellsCellular biologyCoronary ArteriosclerosisDataDevelopmentEndothelial CellsEngineeringEnvironmentEvaluationEventExtracellular FluidFoundationsFunctional disorderGap JunctionsGene TargetingGenetic EngineeringHeartHeart failureInfarctionIschemiaMediatingMediator of activation proteinMesenchymal Stem CellsMessenger RNAMicroRNAsMolecularMolecular BiologyMyocardialMyocardial InfarctionMyocardial IschemiaMyocardial perfusionMyocardiumNatural regenerationPathologyPlayPositioning AttributeProteinsReperfusion InjuryResearchRoleStagingStem cell transplantStem cellsTechniquesTestingTherapeuticTissuesTranslational RepressionTransplantationUntranslated RNAUp-RegulationVentricular Remodelingadult stem cellangiogenesisbaseblood vessel developmentcardiac regenerationcardiac repaircell injurycoronary fibrosisdesignexperienceextracellularimprovedin vivoinsightmolecular imagingnovel therapeuticsoverexpressionregenerativerepairedstem cell biologystem cell therapytissue repairtranscription factor
项目摘要
DESCRIPTION (provided by applicant): Stem cell therapy is a putative treatment for end-stage heart failure. Bone marrow-derived mesenchymal stem cells (MSC) improve cardiac function following intramyocardial transplantation. Our previous study indicates that MSC preprogrammed to express GATA-4 (MSCGATA-4), a well-known cardiac transcription factor, significantly accelerate ischemic heart repair - by increasing MSC survival and differentiation, as
well as angiogenesis. However, the mechanism is unclear. The recently discovered endogenous class of small non-coding RNAs, microRNAs (miRs), plays an important role in both cardiac protection and pathology associated with myocardial ischemia. Our preliminary data indicate that overexpression of GATA-4 in MSC modulates expression of several miRs which can then transfer from MSC into neighboring cardiomyocytes (CM). We propose the following two hypotheses: Hypothesis 1: Specific miRs and miR targeted genes mediate potent pro-survival and pro-angiogenic effects. Hypothesis 2: miRs in transplanted MSC transfer to neighboring host cells or the extracellular environment via gap junctions and microvesicles (MVs). The proposed study represents the first in- depth attempt to elucidate the mechanism by which GATA-4 overexpression in MSC regulates expression of specific miRs that, in turn, enhance angiogenesis and cardioprotection when these MSC are transplanted into ischemic myocardium. The results of these studies should (i) provide evidence that MSC besides their differentiation potential serve as an important delivery vehicle for cardioprotectve proteins and molecules in repair of ischemic myocardium; (ii) explore the impact of transfer of specific molecules from MSC to the extracellular fluid space via MVs, and directly into CM via gap junctions or other intercellular channels. These findings may not only highlight the molecular mechanisms of MSCGATA-4 - mediated angiogenesis, but may also help formulate a novel therapeutic strategy for ischemia and offer insight into the progression of myocardial remodeling.
描述(由申请人提供):干细胞治疗是终末期心力衰竭的公认治疗方法。骨髓间充质干细胞(MSC)心肌内移植后改善心功能我们以前的研究表明,MSC预编程表达加塔-4(MSC加塔-4),一种众所周知的心脏转录因子,通过增加MSC的存活和分化,显著加速缺血性心脏修复,
以及血管生成。然而,其机制尚不清楚。近年来发现的一类内源性小分子非编码RNA(microRNA,miRs)在心肌缺血的病理学和心脏保护中起着重要作用。我们的初步数据表明,MSC中加塔-4的过表达调节了几种miR的表达,这些miR然后可以从MSC转移到邻近的心肌细胞(CM)中。我们提出以下两个假设:假设1:特定的miR和miR靶向基因介导有效的促生存和促血管生成作用。假设2:移植MSC中的miR通过间隙连接和微泡(MV)转移到邻近宿主细胞或细胞外环境。所提出的研究代表了阐明MSC中加塔-4过表达调节特异性miR表达的机制的第一次深入尝试,当这些MSC移植到缺血心肌中时,特异性miR反过来增强血管生成和心脏保护。这些研究的结果应(i)提供证据表明,MSC除了其分化潜力外,还可作为缺血心肌修复中心脏保护蛋白和分子的重要递送载体;(ii)探索特定分子通过MV从MSC转移到细胞外液空间,并通过间隙连接或其他细胞间通道直接进入CM的影响。这些发现不仅可以突出MSCGATA-4介导的血管生成的分子机制,还可以帮助制定一种新的缺血治疗策略,并提供对心肌重塑进展的深入了解。
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)
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Muhammad Ashraf其他文献
Muhammad Ashraf的其他文献
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{{ truncateString('Muhammad Ashraf', 18)}}的其他基金
Innovative Approaches to Treat Duchenne Muscular Dystrophy Using iPSC-Derived Muscle Progenitors
使用 iPSC 衍生的肌肉祖细胞治疗杜氏肌营养不良症的创新方法
- 批准号:
9687673 - 财政年份:2016
- 资助金额:
$ 49.14万 - 项目类别:
Innovative Approaches to Treat Duchenne Muscular Dystrophy Using iPSC-Derived Muscle Progenitors
使用 iPSC 衍生的肌肉祖细胞治疗杜氏肌营养不良症的创新方法
- 批准号:
9232058 - 财政年份:2016
- 资助金额:
$ 49.14万 - 项目类别:
Notch1/miR-322 Axis in Stem Cell Mediated Vascular Repair
Notch1/miR-322 轴在干细胞介导的血管修复中的作用
- 批准号:
9332457 - 财政年份:2016
- 资助金额:
$ 49.14万 - 项目类别:
Notch1/miR-322 Axis in Stem Cell Mediated Vascular Repair
Notch1/miR-322 轴在干细胞介导的血管修复中的作用
- 批准号:
9478676 - 财政年份:2016
- 资助金额:
$ 49.14万 - 项目类别:
Notch1/miR-322 Axis in Stem Cell Mediated Vascular Repair
Notch1/miR-322 轴在干细胞介导的血管修复中的作用
- 批准号:
9923003 - 财政年份:2016
- 资助金额:
$ 49.14万 - 项目类别:
Innovative Approaches to Treat Duchenne Muscular Dystrophy Using iPSC-Derived Muscle Progenitors
使用 iPSC 衍生的肌肉祖细胞治疗杜氏肌营养不良症的创新方法
- 批准号:
10162502 - 财政年份:2016
- 资助金额:
$ 49.14万 - 项目类别:
Integration Free IPS Cells-Derived Progenitors for Cardiac Regeneration
用于心脏再生的免整合 IPS 细胞衍生祖细胞
- 批准号:
8839043 - 财政年份:2015
- 资助金额:
$ 49.14万 - 项目类别:
MicroRNA as mediators of angiogenesis & ischemic myocardial repair
MicroRNA 作为血管生成的介质
- 批准号:
8333130 - 财政年份:2012
- 资助金额:
$ 49.14万 - 项目类别:
MicroRNA as mediators of angiogenesis & ischemic myocardial repair
MicroRNA 作为血管生成的介质
- 批准号:
9059179 - 财政年份:2012
- 资助金额:
$ 49.14万 - 项目类别:
MicroRNA as mediators of angiogenesis & ischemic myocardial repair
MicroRNA 作为血管生成的介质
- 批准号:
8509782 - 财政年份:2012
- 资助金额:
$ 49.14万 - 项目类别:
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