Tissue Engineering Strategies: Effects on Valvular Interstitial Cell Metabolism
组织工程策略:对瓣膜间质细胞代谢的影响
基本信息
- 批准号:8113636
- 负责人:
- 金额:$ 7.63万
- 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:2011-06-01 至 2013-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAdultAffectAmericanAnabolismAnisotropyBehaviorBiologyBiomedical EngineeringBlood VesselsCardiacCardiovascular systemCell CommunicationCell Culture TechniquesCellsCellular biologyCharacteristicsChemical StimulationComplementCongenital AbnormalityDataDevelopmentDiabetes MellitusDiffusionDilatation - actionDiseaseDisease ProgressionDoctor of PhilosophyEngineeringEnvironmentExplosionExtracellular MatrixExtracellular Matrix ProteinsFatty AcidsFeasibility StudiesFrequenciesFutureGene ExpressionGlucoseGlycolysisGlycosaminoglycansGoalsHeart Valve DiseasesHeart ValvesHospitalizationHyaluronanHypoxiaIn VitroIncidenceInfectionInjuryInvestigationKnowledgeMeasuresMechanical StimulationMechanicsMediatingMedicalMetabolicMetabolic syndromeMetabolismMethodsMicroarray AnalysisMyocardiumObesityOperative Surgical ProceduresOxygenOxygen ConsumptionPatternPerfusionPhenotypePreventionPrincipal InvestigatorProcessProductionProteinsPublicationsResearchResearch MethodologyResearch PersonnelRoleScientistSignal TransductionSmooth Muscle MyocytesStagingStimulusStressStretchingTestingTherapeuticTissue EngineeringTissuesTranslatingWorkaortic valve disorderbasecell typecytokineeffective therapyemergency service responderfatty acid metabolismfatty acid oxidationflexibilityin vivoinfancyinterstitial cellmetabolic abnormality assessmentnovelnutrient metabolismoxidationpublic health relevancerepairedresponsestressorsuccesssugartissue support frametool
项目摘要
DESCRIPTION (provided by applicant):
PROJECT SUMMARY Principal Investigator: Kathryn Jane Grande-Allen, Ph.D. Heart valve disease mandates hospitalization for almost 100,000 Americans every year. Although some of the initial causes of valve disease are well recognized, the intermediate cell-mediated disease mechanisms are largely unknown. The only effective treatment for most valve diseases is surgical repair or replacement; there are no medical or therapeutic treatments for the prevention or amelioration of valve disease. The drive to dissect potential disease mechanisms and develop new medical therapies has invigorated research in valve biology. This field is in its infancy, but has nonetheless has witnessed many recent findings about contractile, synthetic, cell communication, adhesion, and signaling characteristics of valvular interstitial cells (VICs), especially as they relate to the tissue engineering of valves and the development of calcific aortic valve disease. Nonetheless, there has been scant investigation into the metabolism of valve cells. Although recent publications have addressed how oxygen diffusion and perfusion affects valve cells and tissue engineered valves, the topic of valvular cell metabolism remains largely unaddressed. Cells within normal adult valves maintain quiescence (even within such a mechanically active tissue), but show the capacity to become activated and alter their phenotype/behavior in response to various injury or disease conditions. This activation process is quite poorly characterized, leading to several questions about the fundamental metabolic rates of VICs under these quiescent and activated conditions. It is also unknown how this metabolic rate is influenced by the environment of the cell, meaning its pericellular matrix and level of mechanical or chemical stimulation. These issues are very important given the use of exogenous stimuli in the development of tissue engineered valves, and the roles of these factors in valve remodeling and disease progression. Indeed, metabolism is recognized as the first responder to environmental stresses for most cell types. To address these questions, this research proposes to determine the fundamental metabolic rates of VICs (Aim 1). The following 2 aims will examine the effect of cytokine and hypoxic stimulation (Aim 2) and mechanical stretch (Aim 3) on metabolic rates and metabolic gene expression by VICs. This research is significant because it will provide new and fundamental information about the metabolic rates of VICs under basal and stressed culture conditions, and will establish an important new direction in the field of valve cell biology. The resulting data will complement the work of other investigators examining oxygen consumption of VICs and valve leaflets, and will guide scientists and engineers developing tissue engineered valves. This work will also promote new avenues for valve disease research, since the valve cell responses (enabled by metabolism) likely contribute to disease progression, whether the initial cause was cardiac dilatation, infection, or a congenital malformation. Information about fatty acid metabolism would be relevant to the early stages of calcific aortic valve disease, since there is a growing incidence of this condition in the setting of obesity, diabetes, and metabolic syndrome.
PUBLIC HEALTH RELEVANCE:
Public Health Relevance Principal Investigator: Kathryn Jane Grande-Allen, Ph.D. Heart valve disease leads to hospitalization for almost 100,000 Americans every year, but the causes of heart valve disease are a mystery, especially because much of the behavior of heart valve cells has never been previously studied. This research will study the metabolism of heart valve cells, meaning how they use sugars, fatty acids, and lactate to create fuel for their activities such as migrating and making new proteins. This research will also examine how several conditions that are used to create tissue engineered heart valves affect this metabolism. This research is also relevant due to the growing incidence of aortic valve disease in the setting of obesity, diabetes, and metabolic syndrome.
描述(由申请人提供):
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 }}
KATHRYN JANE GRANDE-ALLEN其他文献
KATHRYN JANE GRANDE-ALLEN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('KATHRYN JANE GRANDE-ALLEN', 18)}}的其他基金
Differential Shear Forces on Endocardial Endothelial Cells Regulate a Fibrotic Spectrum in the Left Ventricular Outflow Tract
心内膜内皮细胞上的差异剪切力调节左心室流出道中的纤维化谱
- 批准号:
10170409 - 财政年份:2018
- 资助金额:
$ 7.63万 - 项目类别:
Biomimetic micro-structured hydrogel scaffolds for tissue engineered heart valves
用于组织工程心脏瓣膜的仿生微结构水凝胶支架
- 批准号:
8663737 - 财政年份:2011
- 资助金额:
$ 7.63万 - 项目类别:
Biomaterial Strategies for Tissue Engineering Pediatric Valves
组织工程儿科瓣膜的生物材料策略
- 批准号:
8315987 - 财政年份:2011
- 资助金额:
$ 7.63万 - 项目类别:
Tissue Engineering Strategies: Effects on Valvular Interstitial Cell Metabolism
组织工程策略:对瓣膜间质细胞代谢的影响
- 批准号:
8241919 - 财政年份:2011
- 资助金额:
$ 7.63万 - 项目类别:
Biomimetic micro-structured hydrogel scaffolds for tissue engineered heart valves
用于组织工程心脏瓣膜的仿生微结构水凝胶支架
- 批准号:
8250357 - 财政年份:2011
- 资助金额:
$ 7.63万 - 项目类别:
Biomaterial Strategies for Tissue Engineering Pediatric Valves
组织工程儿科瓣膜的生物材料策略
- 批准号:
8178833 - 财政年份:2011
- 资助金额:
$ 7.63万 - 项目类别:
Biomimetic micro-structured hydrogel scaffolds for tissue engineered heart valves
用于组织工程心脏瓣膜的仿生微结构水凝胶支架
- 批准号:
8086246 - 财政年份:2011
- 资助金额:
$ 7.63万 - 项目类别:
相似海外基金
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y004841/1 - 财政年份:2024
- 资助金额:
$ 7.63万 - 项目类别:
Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
- 批准号:
BB/Y001427/1 - 财政年份:2024
- 资助金额:
$ 7.63万 - 项目类别:
Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y005414/1 - 财政年份:2024
- 资助金额:
$ 7.63万 - 项目类别:
Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
- 批准号:
10669829 - 财政年份:2023
- 资助金额:
$ 7.63万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10587090 - 财政年份:2023
- 资助金额:
$ 7.63万 - 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
- 批准号:
10821599 - 财政年份:2023
- 资助金额:
$ 7.63万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10841832 - 财政年份:2023
- 资助金额:
$ 7.63万 - 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
- 批准号:
10532480 - 财政年份:2022
- 资助金额:
$ 7.63万 - 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
- 批准号:
10741261 - 财政年份:2022
- 资助金额:
$ 7.63万 - 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
- 批准号:
10674894 - 财政年份:2022
- 资助金额:
$ 7.63万 - 项目类别: