Gene Therapy for Long-Term Myocardial Protection
长期心肌保护的基因治疗
基本信息
- 批准号:8449674
- 负责人:
- 金额:$ 34.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-05-02 至 2014-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAcute myocardial infarctionAddressAnimalsAnti-Inflammatory AgentsAnti-inflammatoryAntigensAntioxidantsAnusApoptosisApoptoticAreaArrhythmiaAutopsyBerylliumBilirubinBiochemicalBiodistributionBiological AssayBiological MarkersBiological PreservationBloodBrain Hypoxia-IschemiaCarbon MonoxideCardiacCatabolismCathetersCell DeathCell RespirationCell SurvivalClinicalCongestive Heart FailureCoronaryCoronary arteryCytomegalovirusDevelopmentDimensionsDoseDrug Delivery SystemsEchocardiographyEffectivenessElectrolytesElementsEnzymesFamily suidaeFibrosisFlow CytometryFluorescenceFutureGene DeliveryGene TransferGenerationsGenesGoalsHeartHeart DiseasesHemeHemorrhageHistologicHomeostasisHourHumanHypoxiaHypoxia-Responsive ElementsImageInfarctionInflammationInfusion proceduresInjection of therapeutic agentInjuryIntravenousIschemiaKidneyLeft Ventricular FunctionLeft ventricular structureLiverMagnetic Resonance ImagingMaintenanceMature T-LymphocyteMeasurementMeasuresMediatingMembrane PotentialsMetabolicMetabolismMethodsMicrocirculationMicroscopyMitochondriaModelingMolecularMolecular AnalysisMonitorMuscle CellsMyocardialMyocardial InfarctionMyocardial IschemiaMyocardial ReperfusionMyocardiumOrganOrphanOutcomeOxidative StressPathway interactionsPatientsPerformancePerfusionPeripheralPharmaceutical PreparationsPhasePhysiologicalProcessPropertyRandomizedRattusReaction TimeRecovery of FunctionRegulationReperfusion InjuryReperfusion TherapyResistanceRetinoidsReverse Transcriptase Polymerase Chain ReactionRiskRodent ModelRoleRuptureSafetySerotypingSerumSiteStaphylococcal Enterotoxin BStructureStructure of left gastric veinSuperoxide DismutaseSurfaceT cell transcription factor 1T-Cell DevelopmentT-LymphocyteTestisTherapeuticThymus GlandTimeTissue HarvestingTissue SampleTissuesTransgenesTransgenic OrganismsTranslationsTransmission Electron MicroscopyTreatment EfficacyTropismTroponinUniversitiesUp-RegulationValidationVentricularVentricular FunctionViralViral GenomeViral Load resultVirusWeightWestern BlottingWorkadaptive immunityadeno-associated viral vectorallograft rejectionbaseclinical applicationdesigndosageexperienceextracellulargene therapyheme oxygenase-1high riskmitochondrial membranemortalitynoveloutcome forecastpressurepublic health relevancereceptorresearch studyresponsetherapeutic genethymocytetransduction efficiencytransgene expressionvector
项目摘要
DESCRIPTION (provided by applicant): Regulated apoptosis is critical to T cell development in the thymus and controls T cell- dependent adaptive immunity in periphery. 2-catenin, a coactivator of T cell factor 1 (TCF-1), and retinoid-related orphan receptor gamma t (ROR3t) both regulate thymocyte survival via the up-regulation of anti-apoptotic Bcl-xL. In the process of studying ROR3t, we have identified 2- catenin/TCF-1 as a potential upstream pathway that controls ROR3t-mediated thymocyte survival. Deletion of TCF-1 resulted in thymocyte apoptosis and down-regulated ROR3t, whereas transgenic expression of a stabilized 2-catenin (2-catTg), which activated TCF-1 constitutively, led to enhanced thymocyte survival and up-regulated ROR3t. In contrast to its survival role in thymocytes, 2-catTg up-regulated pro-apoptotic Bid and surface Fas, and enhanced super-antigen staphylococcal enterotoxin B (SEB)-induced deletion of peripheral T cells by promoting activation-induced cell death (AICD). We thus hypothesize that the 2- catenin/TCF pathway utilizes distinct mechanisms in the regulation of apoptosis in developing T cells and peripheral mature T cells. In the first two aims of this study, we propose to elucidate the mechanisms responsible for 2-catenin/TCF-1-regulated apoptosis in thymocytes and peripheral T cells. In the last aim, we will determine whether we can control T cell-dependent allograft rejection by manipulating 2-catenin-regulated T cell survival.
描述(由申请方提供):调节性细胞凋亡对胸腺中的T细胞发育至关重要,并控制外周中的T细胞依赖性适应性免疫。2-连环蛋白,T细胞因子1(TCF-1)的共激活物,和类维生素A相关孤儿受体γ t(ROR 3 t)都通过上调抗凋亡Bcl-xL来调节胸腺细胞存活。在研究ROR 3 t的过程中,我们已经确定2- catenin/TCF-1作为控制ROR 3 t介导的胸腺细胞存活的潜在上游通路。TCF-1的缺失导致胸腺细胞凋亡并下调ROR 3 t,而稳定的2-catenin(2-catTg)的转基因表达(组成性激活TCF-1)导致胸腺细胞存活增强并上调ROR 3 t。与其在胸腺细胞中的存活作用相反,2-catTg上调促凋亡Bid和表面Fas,并通过促进活化诱导的细胞死亡(AICD)增强超抗原葡萄球菌肠毒素B(SE B)诱导的外周T细胞缺失。因此,我们假设2-连环蛋白/TCF途径在发育中的T细胞和外周成熟T细胞的凋亡调节中利用不同的机制。在本研究的前两个目的中,我们建议阐明2-catenin/TCF-1调节胸腺细胞和外周T细胞凋亡的机制。在最后一个目标中,我们将确定是否可以通过操纵2-连环蛋白调节的T细胞存活来控制T细胞依赖性同种异体移植排斥反应。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
MicroRNAs and Cardiac Regeneration.
microRNA和心脏再生。
- DOI:10.1161/circresaha.116.304377
- 发表时间:2015-05-08
- 期刊:
- 影响因子:20.1
- 作者:Hodgkinson CP;Kang MH;Dal-Pra S;Mirotsou M;Dzau VJ
- 通讯作者:Dzau VJ
MicroRNA induced cardiac reprogramming in vivo: evidence for mature cardiac myocytes and improved cardiac function.
MicroRNA在体内诱导心脏重编程:成熟心肌细胞和改善心脏功能的证据。
- DOI:10.1161/circresaha.116.304510
- 发表时间:2015-01-30
- 期刊:
- 影响因子:20.1
- 作者:Jayawardena TM;Finch EA;Zhang L;Zhang H;Hodgkinson CP;Pratt RE;Rosenberg PB;Mirotsou M;Dzau VJ
- 通讯作者:Dzau VJ
Demethylation of H3K27 Is Essential for the Induction of Direct Cardiac Reprogramming by miR Combo.
- DOI:10.1161/circresaha.116.308741
- 发表时间:2017-04-28
- 期刊:
- 影响因子:20.1
- 作者:Dal-Pra S;Hodgkinson CP;Mirotsou M;Kirste I;Dzau VJ
- 通讯作者:Dzau VJ
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Victor J Dzau其他文献
Strategic imperatives for health in the USA: a roadmap for the incoming presidential administration
美国健康领域的战略要务:新总统政府的路线图
- DOI:
10.1016/s0140-6736(24)02189-5 - 发表时间:
2024-12-07 - 期刊:
- 影响因子:88.500
- 作者:
Victor J Dzau;Melissa H Laitner;Emily L Shambaugh - 通讯作者:
Emily L Shambaugh
276 ANDROGEN REGULATES SUBMANDIBULAR GLAND (SMG) RENIN SYNTHESIS AND SECRETICN AT MULTIPLE SITES
- DOI:
10.1203/00006450-198504000-00306 - 发表时间:
1985-04-01 - 期刊:
- 影响因子:3.100
- 作者:
Julie R Ingelfinger;Richard E Pratt;Timothy P Roth;Victor J Dzau - 通讯作者:
Victor J Dzau
Health-care workforce implications of the emDobbs v Jackson Women's Health Organization/em decision
emDobbs 诉杰克逊妇女健康组织案裁决对医疗保健劳动力的影响
- DOI:
10.1016/s0140-6736(24)00581-6 - 发表时间:
2024-06-22 - 期刊:
- 影响因子:88.500
- 作者:
Claire D Brindis;Melissa H Laitner;Ellen Wright Clayton;Susan C Scrimshaw;Barbara J Grosz;Lisa A Simpson;Sara Rosenbaum;Corale L Brierley;Melissa A Simon;Yvette Roubideaux;Bruce N Calonge;Paula A Johnson;Laura DeStefano;Ashley Bear;Kavita S Arora;Victor J Dzau - 通讯作者:
Victor J Dzau
Societal implications of the emDobbs v Jackson Women's Health Organization/em decision
多布斯诉杰克逊妇女健康组织案判决的社会影响
- DOI:
10.1016/s0140-6736(24)00534-8 - 发表时间:
2024-06-22 - 期刊:
- 影响因子:88.500
- 作者:
Claire D Brindis;Melissa H Laitner;Ellen Wright Clayton;Susan C Scrimshaw;Barbara J Grosz;Lisa A Simpson;Sara Rosenbaum;Corale L Brierley;Melissa A Simon;Yvette Roubideaux;Bruce N Calonge;Paula A Johnson;Laura DeStefano;Ashley Bear;Kavita S Arora;Victor J Dzau - 通讯作者:
Victor J Dzau
406-1 Hypoxia regulatable Aav-2 vector protects against cardiac ischemia/reperfusion injury
- DOI:
10.1016/s0735-1097(04)92260-7 - 发表时间:
2004-03-03 - 期刊:
- 影响因子:
- 作者:
Alok S Pachori;Luis G Melo;Lunan Zhang;Richard E Pratt;Victor J Dzau - 通讯作者:
Victor J Dzau
Victor J Dzau的其他文献
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{{ truncateString('Victor J Dzau', 18)}}的其他基金
Novel strategy for Enhancing miRNA as a Therapeutic for Cardiac Regeneration
增强 miRNA 作为心脏再生治疗的新策略
- 批准号:
9237608 - 财政年份:2016
- 资助金额:
$ 34.74万 - 项目类别:
MYOCARDIAL PROTECTION OF HASF IN ACUTE MI
HASF 对急性心肌梗死的心肌保护作用
- 批准号:
8363208 - 财政年份:2011
- 资助金额:
$ 34.74万 - 项目类别:
Sfrp2 and Cardiac Progenitor Cells in Regenerative Response to Ischemic Injury
Sfrp2 和心脏祖细胞对缺血性损伤的再生反应
- 批准号:
8239268 - 财政年份:2006
- 资助金额:
$ 34.74万 - 项目类别:
Sfrp2 as a Stem Cell Derived Paracrine Factor for Cardioprotection
Sfrp2 作为干细胞衍生的旁分泌因子,具有心脏保护作用
- 批准号:
7145291 - 财政年份:2006
- 资助金额:
$ 34.74万 - 项目类别:
Sfrp2 and Cardiac Progenitor Cells in Regenerative Response to Ischemic Injury
Sfrp2 和心脏祖细胞对缺血性损伤的再生反应
- 批准号:
8590214 - 财政年份:2006
- 资助金额:
$ 34.74万 - 项目类别:
Sfrp2 as a Stem Cell Derived Paracrine Factor for Cardioprotection
Sfrp2 作为干细胞衍生的旁分泌因子,具有心脏保护作用
- 批准号:
7642490 - 财政年份:2006
- 资助金额:
$ 34.74万 - 项目类别:
Sfrp2 and Cardiac Progenitor Cells in Regenerative Response to Ischemic Injury
Sfrp2 和心脏祖细胞对缺血性损伤的再生反应
- 批准号:
8786586 - 财政年份:2006
- 资助金额:
$ 34.74万 - 项目类别:
Sfrp2 as a Stem Cell Derived Paracrine Factor for Cardioprotection
Sfrp2 作为干细胞衍生的旁分泌因子,具有心脏保护作用
- 批准号:
7446063 - 财政年份:2006
- 资助金额:
$ 34.74万 - 项目类别:
Sfrp2 as a Stem Cell Derived Paracrine Factor for Cardioprotection
Sfrp2 作为干细胞衍生的旁分泌因子,具有心脏保护作用
- 批准号:
7286054 - 财政年份:2006
- 资助金额:
$ 34.74万 - 项目类别:
Sfrp2 and Cardiac Progenitor Cells in Regenerative Response to Ischemic Injury
Sfrp2 和心脏祖细胞对缺血性损伤的再生反应
- 批准号:
8403716 - 财政年份:2006
- 资助金额:
$ 34.74万 - 项目类别:
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