Bioenergetics in Hypertrophied and Remodeled Left Ventricle
左心室肥厚和重塑的生物能学
基本信息
- 批准号:9162316
- 负责人:
- 金额:$ 58万
- 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:2012-08-10 至 2017-07-31
- 项目状态:已结题
- 来源:
- 关键词:ATP phosphohydrolaseAllogenicAnimal ModelBioenergeticsBlood VesselsBlood flowBuffersCardiacCell Differentiation processCell TransplantationCellsClinical TrialsCongestive Heart FailureContractsCoronary ArteriosclerosisCoronary StenosisCoronary arteryCoronary heart diseaseCreatine KinaseDiagnosticEnergy MetabolismEngraftmentEtiologyFamily suidaeFunctional disorderGrowth FactorHeartHeart TransplantationHypertrophyInfarctionIschemiaLeadLeftLeft Ventricular HypertrophyLeft Ventricular RemodelingLeft ventricular structureMagnetic Resonance ImagingMeasuresMesenchymal Stem Cell TransplantationMesenchymal Stem CellsMethodsModalityModelingMolecular ProfilingMuscle CellsMyocardialMyocardial ContractionMyocardial InfarctionMyocardial perfusionMyocardiumNatural regenerationOxidative StressPathway interactionsPatientsPerformancePerfusionPost-Translational Protein ProcessingPre-Clinical ModelProductionProtein FamilyProteinsProteomicsReportingResearchSafetySecondary toSeveritiesSignal PathwayStem cell transplantStressSystemSystoleTherapeuticTimeVentricularbaseclinically relevantcomparativedata acquisitiondensitydesigndifferential expressionfollow-upfunctional outcomesimprovedin vivointerestliquid chromatography mass spectrometrypressurepreventprotein expressionrepairedresearch studyresponsesexstem cells
项目摘要
DESCRIPTION (provided by applicant): The inner layers of the left ventricular wall (ENDO) are known to be the most susceptible to oxidative stresses. We hypothesize that there is transmural gradient of reserves of ATP production rate via both creatine kinase (CK) and ATPase, which is the lowest in ENDO that results in the ENDO vulnerability in LVH hearts. Despite the intense interest in cellular therapy for myocardial repair, the majority of research reports to date have been designed to repair or prevent LV dysfunction in hearts with myocardial infarction secondary to coronary arteries diseases. Given the fact that more than 50% of heart transplant CHF patients whose etiology is nonischemic, studies using nonischemic large animal model is urgently needed before pursuing large scale clinical trials. The mechanisms underlying the beneficial effects of cellular therapy are not well defined. It is a consistent finding that the engraftment rate is low. However, the long term improvement of the LV contractile function of the recipient heart is consistently observed. Therefore, in addition to the myocardial regeneration from the engrafted cells the improved LV chamber function is also likely related to the changes of the recipient myocardial protein deferential expression. Comparing two swine models of LVH secondary to pressure overload or to postinfarction LV remodeling, the effects of MSCs transplantation on LV contractile function (MRI); myocardial perfusion, myocardial oxygenation level (1H-MRS); and ATP turnover rate (31P- MRS) will be measured biweekly for 8 weeks, the recipient myocardial differential protein expression will be examined by comparative proteomics. The specific aims are: SA1. Using the recently developed T1-nom P-31 magnetization saturation transfer (MST) methods to examine whether the myocardial ATP turnover rate via CK and ATPase are most severely altered in the ENDO of LVH hearts, and whether the severity of which is linearly related to the severity of the LV dysfunction. SA2. To examine whether the functional beneficial effects of allogenic MSC transplantation are accompanied by the improvement of ATP production capacity via CK and ATPase in the ENDO of LVH hearts with or without ischemic coronary artery diseases, and whether these functional benefits are accompanied by regeneration of myocardium from both engrafted MSCs as well as endogenous CPCs. SA3: To examine whether the functional beneficial effects of cellular therapy are associated with the differential protein expression profle of the recipient myocardium. We will employ cutting edge liquid chromatography mass spectrometry-based comparative proteomics method to quantitatively determine the changes in the protein expression with a special emphasis on growth factors family proteins and proteins involved in energy metabolism. The findings of the experiments will elucidate for the first time, the transmural gradient of ATP turnover rate via both CK and ATPase in the in vivo LVH hearts. The findings of these studies will advance our understanding of the mechanisms of cellular therapy in myocardial repair, and lead to better diagnostic and therapeutic modalities for CHF patients.
描述(申请人提供):众所周知,左室壁(Endo)的内层最容易受到氧化应激的影响。我们假设通过肌酸激酶(CK)和ATPase的ATP产生率的储备存在跨壁梯度,而后者是Endo中最低的,导致LVH心脏的Endo易损性。尽管细胞疗法对心肌修复有着浓厚的兴趣,但到目前为止,大多数研究报告都是为了修复或预防继发于冠状动脉疾病的心肌梗死患者的左心功能障碍。鉴于超过50%的心脏移植CHF患者的病因是非缺血性的,在进行大规模临床试验之前,迫切需要使用非缺血性大动物模型进行研究。细胞疗法的有益效果的潜在机制还没有很好的定义。植入率很低,这是一致的发现。然而,受体心脏的左心室收缩功能的长期改善是始终如一的。因此,除了移植细胞的心肌再生外,LV腔功能的改善也可能与受体心肌蛋白表达的变化有关。比较两种压力超负荷或心肌梗死后左室重构所致的猪左室肥厚模型,移植MSCs对左心室收缩功能(MRI)、心肌血流灌注、心肌氧合水平(1H-MRS)和三磷酸腺苷(31P-MRS)的影响,用比较蛋白质组学方法检测受体心肌的差异蛋白表达。具体目标是:SA1。应用新近发展的T1-NOM P-31磁化饱和转移(MST)方法,检测心肌细胞通过CK和ATPase的ATP转换率是否在LVH心脏的内分泌发生了最严重的改变,其严重程度是否与LV功能障碍的严重程度呈线性相关。SA2.目的:探讨同种异体骨髓间充质干细胞移植的功能益处是否伴随有或不伴有缺血性冠状动脉病变的左室肥厚心脏内皮细胞通过CK和ATPase产生三磷酸腺苷能力的提高,以及这些功能益处是否伴随着移植的骨髓间充质干细胞和内源性星形胶质细胞的心肌再生。SA3:研究细胞治疗的功能益处是否与受体心肌的差异蛋白表达有关。我们将利用尖端的液-质联用比较蛋白质组学方法来定量确定蛋白质表达的变化,重点是生长因子、家族蛋白质和参与能量代谢的蛋白质。这些实验结果将首次阐明在体左室肥厚心脏中,通过CK和ATPase实现的ATP转换率的跨壁梯度。这些研究的结果将促进我们对细胞治疗在心肌修复中的机制的理解,并为CHF患者提供更好的诊断和治疗方法。
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 }}
Jianyi Zhang其他文献
Jianyi Zhang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('Jianyi Zhang', 18)}}的其他基金
Project 1 - Endogenous and Exogenous Mechanisms that Promote Myocardial Remuscularization
项目 1 - 促进心肌再肌化的内源性和外源性机制
- 批准号:
10677730 - 财政年份:2022
- 资助金额:
$ 58万 - 项目类别:
Project 1 - Endogenous and Exogenous Mechanisms that Promote Myocardial Remuscularization
项目 1 - 促进心肌再肌化的内源性和外源性机制
- 批准号:
10493838 - 财政年份:2022
- 资助金额:
$ 58万 - 项目类别:
Mechanisms that Govern Cardiomyocyte Proliferation and Remuscularization following Ventricular Injury
心室损伤后控制心肌细胞增殖和再肌化的机制
- 批准号:
10493834 - 财政年份:2022
- 资助金额:
$ 58万 - 项目类别:
Mechanisms that Govern Cardiomyocyte Proliferation and Remuscularization following Ventricular Injury
心室损伤后控制心肌细胞增殖和再肌化的机制
- 批准号:
10677719 - 财政年份:2022
- 资助金额:
$ 58万 - 项目类别:
Bioenergetics in Hypertrophied and Remodeled Left Ventricle
左心室肥厚和重塑的生物能学
- 批准号:
8676931 - 财政年份:2012
- 资助金额:
$ 58万 - 项目类别:
Cell Therapy in Hypertrophied and Remodeled Left Ventricle
左心室肥大和重塑的细胞疗法
- 批准号:
9391517 - 财政年份:2012
- 资助金额:
$ 58万 - 项目类别:
Endogenous and exogenous mechanisms that promote myocardial remuscularization in post infarction LV remodeling
梗死后左室重构中促进心肌再肌化的内源性和外源性机制
- 批准号:
10302748 - 财政年份:2012
- 资助金额:
$ 58万 - 项目类别:
Bioenergetics in Hypertrophied and Remodeled Left Ventricle
左心室肥厚和重塑的生物能学
- 批准号:
8528711 - 财政年份:2012
- 资助金额:
$ 58万 - 项目类别:
相似海外基金
HLA-homozygous iPSC-cardiomyocytE Aggregate manufacturing technoLogies for allogenic cell therapy to the heart (HEAL)
HLA-纯合 iPSC-心肌细胞 用于心脏同种异体细胞治疗 (HEAL) 的聚集体制造技术
- 批准号:
10039902 - 财政年份:2022
- 资助金额:
$ 58万 - 项目类别:
EU-Funded
Evaluation of the efficacy of LAT1 inhibitor to tumor stroma and immunity in an allogenic mouse model of colon cancer having abundant stroma.
在具有丰富基质的同种异体结肠癌小鼠模型中评估 LAT1 抑制剂对肿瘤基质和免疫的功效。
- 批准号:
21K15925 - 财政年份:2021
- 资助金额:
$ 58万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mechanism of kidney injury associated with graft-versus-host disease after allogenic stem cell transplantation
同种异体干细胞移植后移植物抗宿主病相关肾损伤的机制
- 批准号:
21K08410 - 财政年份:2021
- 资助金额:
$ 58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Clarification of the origin and maintenance mechanisms of junctional epithelium and identification of its stem cells using allogenic tooth germ transplantation
阐明交界上皮的起源和维持机制并利用同种异体牙胚移植鉴定其干细胞
- 批准号:
20K21672 - 财政年份:2020
- 资助金额:
$ 58万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
The study about the allogenic MSCs transplantation to the cardiac disease models.
同种异体间充质干细胞移植至心脏病模型的研究。
- 批准号:
18K16395 - 财政年份:2018
- 资助金额:
$ 58万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Artificial nerves containing allogenic basal lamellae scaffold and bone marrow derived stem cells
含有同种异体基底板层支架和骨髓干细胞的人工神经
- 批准号:
17K10951 - 财政年份:2017
- 资助金额:
$ 58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Role of HSP90-alpha in preserving immunoprivilege of allogenic mesenchymal stem cells in the ischemic heart
HSP90-α 在保护缺血心脏同种异体间充质干细胞免疫特权中的作用
- 批准号:
370541 - 财政年份:2017
- 资助金额:
$ 58万 - 项目类别:
Operating Grants
Attempt to Prefabricate Vascularized Allogenic Bone in Recipient -Use of Cultured Bone Marrow Cells-
尝试在受者体内预制血管化的同种异体骨 - 使用培养的骨髓细胞 -
- 批准号:
16K10863 - 财政年份:2016
- 资助金额:
$ 58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Allogenic micobiota-reconstitution (AMR) for the treatment of patients with diarhea-predominant irritable bowel syndrome (IBS-D) - the AMIRA trial
同种异体微生物群重建 (AMR) 用于治疗腹泻型肠易激综合征 (IBS-D) 患者 - AMIRA 试验
- 批准号:
276706135 - 财政年份:2015
- 资助金额:
$ 58万 - 项目类别:
Clinical Trials
Induction of thyme epithelial cells from iPS cells and application to allogenic transplantation
iPS细胞诱导百里香上皮细胞及其在同种异体移植中的应用
- 批准号:
15H04915 - 财政年份:2015
- 资助金额:
$ 58万 - 项目类别:
Grant-in-Aid for Scientific Research (B)