Alpha-1-Adrenergic Receptor Subtypes in the Cells of the Human Heart
人类心脏细胞中的 Alpha-1-肾上腺素能受体亚型
基本信息
- 批准号:8496578
- 负责人:
- 金额:$ 13.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-01 至 2014-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdrenergic ReceptorAffectAgonistAmericanAnimal ModelAnimalsAreaAttentionBindingBiological AssayBiologyCaliforniaCardiacCardiac MyocytesCardiologyCatecholaminesCell DeathCellsCessation of lifeClinicalCoronaryCoronary arteryDataDevelopmentDiseaseDrug or chemical Tissue DistributionEndothelial CellsFibroblastsFibrosisFosteringFoundationsGoalsHeartHeart HypertrophyHeart failureHumanHypertrophyInstitutionInternal MedicineInvestigationIschemic PreconditioningKnockout MiceKnowledgeLaboratoriesMediatingMedical centerMedicineMentorsMolecularMusMuscle CellsMyocardiumPhysiciansPhysiologicalPlayPrincipal InvestigatorProcessResearchResearch PersonnelResourcesRoleSamplingSan FranciscoScienceScientistSmooth Muscle MyocytesSystemTestingTissue BankingTissue BanksTissue ModelTissuesToxic effectTrainingTraining ProgramsUniversitiesWorkabstractingalpha-1 adrenergic receptorsanimal databeta-adrenergic receptorcareercareer developmentcell typedesignexperienceheart cellmouse modelnovelprogramsreceptorskillssuccesstoolvasoconstriction
项目摘要
DESCRIPTION (provided by applicant): This proposal outlines a 5-year training plan designed to equip the applicant with tools that will foster his success as an academic investigator with a focus on translational heart failure (HF) research. He has completed rigorous clinical training in both internal medicine and cardiology and has spent the past two years acquiring experience in molecular cardiology in the mentor's laboratory. He is now poised for a career in academic medicine, and the proposed program offers an exceptional opportunity to promote his development into an independent physician-scientist. The mentor, Dr. Paul Simpson, will oversee the project and the career development of the applicant. Dr. Simpson is highly respected in the field of molecular cardiology and internationally-recognized for his contributions to our understanding of cardiac hypertrophy and alpha-1-adrenergic receptor (AR) biology. He also is a trained cardiologist who has guided the successful development of many physician-scientists, hence he is a perfect mentor for this project. UCSF is an ideal setting for the proposed training program, offering expertise in nearly every area of biomedical science, and there is a deep commitment from the institution to the development of the applicant as an independent investigator. The research plan follows naturally from the applicant's recent novel work identifying the tissue distribution of the 3 alpha-1-AR subtypes in the human heart. Abundant data from animal studies, including knockout mouse models created by the mentor, show that the alpha-1 A and alpha-IB subtypes play beneficial roles in the heart and protect against HF. Surprisingly, the function of the human cardiac alpha-1-AR subtypes is unknown, and alpha-1-ARs have never been studied in human heart cells. To address these significant gaps in our knowledge, we propose the following 3 Specific Aims: (I) Maintain and expand the UCSF/San Francisco VA Human Heart Tissue Bank; (M) Identify the alpha-1-AR subtypes in myocytes and fibroblasts from non-failing and failing human hearts, and test their function using isolated cell and whole tissue models; (III) Identify the functional alpha-1-AR subtypes in human coronary smooth muscle and endothelial cells. Collectively these Aims will establish a broader understanding of human cardiac alpha-1-AR biology and the mechanisms of HF. This training program will provide the applicant with valuable skills that will allow him to use human systems to test hypotheses generated in animal models and will serve as the foundation for a successful career in translational HF investigation. RELEVANCE: Abundant data from cell and animal studies show that alpha-1-adrenergic receptors (ARs) play beneficial roles in the heart and protect against heart failure (HF), but little is known about these receptors in the human heart. HF is a major clinical problem in the US, and new treatments are badly needed. The proposed work will expand significantly our knowledge of alpha-1-ARs in the human heart and is essential to the long-term aim of the project, which is the development of a novel therapy for HF targeting alpha-1-ARs. (End of abstract)
描述(由申请人提供):该提案概述了一项为期 5 年的培训计划,旨在为申请人提供工具,以促进其作为专注于转化性心力衰竭 (HF) 研究的学术研究者取得成功。他完成了严格的内科和心脏病学临床培训,并在过去两年中在导师的实验室中积累了分子心脏病学的经验。他现在准备从事学术医学事业,拟议的项目提供了一个绝佳的机会,促进他发展成为一名独立的医师科学家。导师保罗·辛普森博士将监督该项目和申请人的职业发展。辛普森博士在分子心脏病学领域备受尊敬,并因其对心脏肥大和 α-1-肾上腺素能受体 (AR) 生物学的理解做出的贡献而获得国际认可。他也是一位训练有素的心脏病专家,指导了许多医师科学家的成功发展,因此他是该项目的完美导师。加州大学旧金山分校是拟议培训计划的理想环境,提供生物医学科学几乎每个领域的专业知识,并且该机构对申请人作为独立研究者的发展做出了坚定的承诺。该研究计划自然地源自申请人最近确定人类心脏中 3 种 α-1-AR 亚型的组织分布的新颖工作。来自动物研究的大量数据,包括导师创建的基因敲除小鼠模型,表明 alpha-1 A 和 alpha-IB 亚型对心脏发挥有益作用,并可预防心力衰竭。令人惊讶的是,人类心脏 α-1-AR 亚型的功能尚不清楚,并且从未在人类心脏细胞中研究过 α-1-AR。为了弥补我们知识上的这些重大差距,我们提出以下 3 个具体目标: (I) 维持和扩大 UCSF/旧金山 VA 人类心脏组织库; (M) 鉴定来自非衰竭和衰竭人类心脏的肌细胞和成纤维细胞中的 α-1-AR 亚型,并使用分离的细胞和整个组织模型测试其功能; (III) 鉴定人冠状平滑肌和内皮细胞中的功能性α-1-AR亚型。总的来说,这些目标将建立对人类心脏 α-1-AR 生物学和心力衰竭机制的更广泛的理解。该培训计划将为申请人提供宝贵的技能,使他能够使用人体系统来测试动物模型中产生的假设,并将为转化性心力衰竭研究的成功职业生涯奠定基础。相关性:来自细胞和动物研究的大量数据表明,α-1-肾上腺素能受体 (AR) 在心脏中发挥有益作用,并可预防心力衰竭 (HF),但人们对人类心脏中的这些受体知之甚少。心力衰竭是美国的一个主要临床问题,迫切需要新的治疗方法。拟议的工作将显着扩展我们对人类心脏中 α-1-AR 的了解,对于该项目的长期目标至关重要,即开发一种针对 α-1-AR 的心力衰竭新疗法。 (摘要结束)
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Skin deep: what can the study of dermal fibroblasts teach us about dilated cardiomyopathy?
深入浅出:真皮成纤维细胞的研究可以告诉我们有关扩张型心肌病的什么信息?
- DOI:
- 发表时间:2010-04
- 期刊:
- 影响因子:5
- 作者:Jensen BC
- 通讯作者:Jensen BC
Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells.
人心外膜冠状动脉内皮细胞上的功能性 α-1B 肾上腺素受体。
- DOI:
- 发表时间:2010-12
- 期刊:
- 影响因子:0
- 作者:Jensen, Brian C;Swigart, Philip M;Montgomery, Megan D;Simpson, Paul C
- 通讯作者:Simpson, Paul C
The alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid and endocannabinoid metabolites associated with inflammation in vivo.
α-1A 肾上腺素受体激动剂 A61603 可减少与体内炎症相关的心脏多不饱和脂肪酸和内源性大麻素代谢物。
- DOI:
- 发表时间:2016-10
- 期刊:
- 影响因子:0
- 作者:Willis, Monte S;Ilaiwy, Amro;Montgomery, Megan D;Simpson, Paul C;Jensen, Brian C
- 通讯作者:Jensen, Brian C
β1‐ and β2‐Adrenergic‐Receptor Subpopulations in Nonfailing and Failing Human Ventricular Myocardium: Coupling of Both Receptor Subtypes to Muscle Contraction and Selective β1‐Receptor Down‐Regulation in Heart Failure
正常和衰竭人类心室心肌中的β1-和β2-肾上腺素受体亚群:两种受体亚型与肌肉收缩的耦合和选择性β1-受体下调-心力衰竭的调节
- DOI:10.1161/circresaha.107.169011
- 发表时间:1986-09-01
- 期刊:
- 影响因子:20.1
- 作者:M. Bristow;R. Ginsburg;V. Umans;M. Fowler;W. Minobe;R. Rasmussen;P. Zera;R. Menlove;P. Shah;S. Jamieson;E. Stinson
- 通讯作者:E. Stinson
Time and technology will tell: the pathophysiologic basis of neurohormonal modulation in heart failure.
- DOI:10.1016/j.hfc.2014.07.002
- 发表时间:2014-10
- 期刊:
- 影响因子:3.4
- 作者:Reed BN;Street SE;Jensen BC
- 通讯作者:Jensen BC
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Brian C Jensen其他文献
Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function
新型泛 ERR 激动剂通过增强心脏脂肪酸代谢和线粒体功能改善心力衰竭
- DOI:
10.1161/circulationaha.123.066542 - 发表时间:
2023-11-14 - 期刊:
- 影响因子:37.8
- 作者:
Weiyi Xu;C. Billon;Hui Li;Andrea Wilderman;Lei Qi;A. Graves;Jernie Rae Rideb;Yuanbiao Zhao;Matthew E. Hayes;Keyang Yu;McKenna Losby;Carissa S Hampton;Christiana M Adeyemi;S. J. Hong;Eleni Nasiotis;Chen Fu;Tae Gyu Oh;Weiwei Fan;M. Downes;Ryan D. Welch;Ronald M. Evans;Aleks;ar Milosavljevic;ar;John K. Walker;Brian C Jensen;Liming Pei;Thomas Burris;Lilei Zhang - 通讯作者:
Lilei Zhang
The nuclear receptor RORα protects against angiotensin II-induced cardiac hypertrophy and heart failure.
核受体 RORα 可防止血管紧张素 II 诱导的心脏肥大和心力衰竭。
- DOI:
10.1152/ajpheart.00531.2018 - 发表时间:
2019-01-01 - 期刊:
- 影响因子:0
- 作者:
J. Beak;H. S. Kang;Wei Huang;Page H Myers;Dawn Bowles;A. Jetten;Brian C Jensen - 通讯作者:
Brian C Jensen
The nuclear receptor RORα preserves cardiomyocyte mitochondrial function by regulating mitophagy through caveolin-3
核受体 RORα 通过 Caveolin-3 调节线粒体自噬来保护心肌细胞线粒体功能
- DOI:
10.1101/2020.10.02.323410 - 发表时间:
2020-10-02 - 期刊:
- 影响因子:0
- 作者:
Brian C Jensen;J. Beak;H. S. Kang;Wei Huang;A. Aghajanian;Kevin Gerrish;A. Jetten - 通讯作者:
A. Jetten
Doxorubicin Exposure Causes Subacute Cardiac Atrophy Dependent on the Striated Muscle–Specific Ubiquitin Ligase MuRF1
暴露于阿霉素会导致依赖于横纹肌的亚急性心肌萎缩——特异性泛素连接酶 MuRF1
- DOI:
10.1161/circheartfailure.118.005234 - 发表时间:
2019-03-01 - 期刊:
- 影响因子:0
- 作者:
M. Willis;Traci L Parry;David I. Brown;Roberto I. Mota;Wei Huang;J. Beak;Michael Sola;Cynthia Zhou;Sean T. Hicks;M. Caughey;Ralph B. D'Agostino;J. Jordan;W. Hundley;Brian C Jensen - 通讯作者:
Brian C Jensen
Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.
抑郁症状与射血分数降低的心力衰竭的临床结果相关。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:3.8
- 作者:
Andrew Sherwood;James A. Blumenthal;R. Mentz;Gary G Koch;Joseph G. Rogers;Patricia P Chang;Christopher Chien;Kirkwood F Adams;Lisa J Rose;Brian C Jensen;Mark Donahue;Kristy S. Johnson;A. Hinderliter - 通讯作者:
A. Hinderliter
Brian C Jensen的其他文献
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{{ truncateString('Brian C Jensen', 18)}}的其他基金
Defining the role of mitochondrial injury in MEK inhibitor cardiotoxicity
确定线粒体损伤在 MEK 抑制剂心脏毒性中的作用
- 批准号:
10753009 - 财政年份:2023
- 资助金额:
$ 13.24万 - 项目类别:
Metabolic mechanisms of cardioprotection through alpha-1A adrenergic receptor activation
通过 α-1A 肾上腺素受体激活保护心脏的代谢机制
- 批准号:
10318139 - 财政年份:2017
- 资助金额:
$ 13.24万 - 项目类别:
Metabolic mechanisms of cardioprotection through alpha-1A adrenergic receptor activation
通过 α-1A 肾上腺素受体激活保护心脏的代谢机制
- 批准号:
10587727 - 财政年份:2017
- 资助金额:
$ 13.24万 - 项目类别:
Metabolic mechanisms of cardioprotection through alpha-1A adrenergic receptor activation
通过 α-1A 肾上腺素受体激活保护心脏的代谢机制
- 批准号:
10067377 - 财政年份:2017
- 资助金额:
$ 13.24万 - 项目类别:
Alpha-1-Adrenergic Receptor Subtypes in the Cells of the Human Heart
人类心脏细胞中的 Alpha-1-肾上腺素能受体亚型
- 批准号:
7919951 - 财政年份:2009
- 资助金额:
$ 13.24万 - 项目类别:
Alpha-1-Adrenergic Receptor Subtypes in the Cells of the Human Heart
人类心脏细胞中的 Alpha-1-肾上腺素能受体亚型
- 批准号:
8131703 - 财政年份:2009
- 资助金额:
$ 13.24万 - 项目类别:
Alpha-1-Adrenergic Receptor Subtypes in the Cells of the Human Heart
人类心脏细胞中的 Alpha-1-肾上腺素能受体亚型
- 批准号:
7707444 - 财政年份:2009
- 资助金额:
$ 13.24万 - 项目类别:
Alpha-1-Adrenergic Receptor Subtypes in the Cells of the Human Heart
人类心脏细胞中的 Alpha-1-肾上腺素能受体亚型
- 批准号:
8294717 - 财政年份:2009
- 资助金额:
$ 13.24万 - 项目类别:
Alpha-1-Adrenergic Receptor Subtypes in the Cells of the Human Heart
人类心脏细胞中的 Alpha-1-肾上腺素能受体亚型
- 批准号:
8294717 - 财政年份:2009
- 资助金额:
$ 13.24万 - 项目类别:
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