Effect of sarcolemmal KATP channels on ROS/RNS generation and calcium handling

肌膜 KATP 通道对 ROS/RNS 生成和钙处理的影响

• 批准号: 8496577
• 负责人: Richard J Gumina
• 金额: $ 12.02万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8496577
• 关键词: ATP sensitive potassium channel complex; Advisory Committees; Affect; Animals; Award; Biochemical; Biology; Calcium; Cardiac; Cardiac Myocytes; Cardiology; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Clinical; Diastolic blood pressure; Doctor of Medicine; Doctor of Philosophy; Etiology; Female; Generations; Genes; Heart; Homeostasis; Human; Hyperbaric Oxygenation; Image; Imaging Techniques; Imaging technology; Injury; Investigational Therapies; Ischemia; Knock-out; Knowledge; Laboratories; Lung; Magnetic Resonance Imaging; Mediating; Mediator of activation protein; Medicine; Mentors; Metabolic; Methods; Modification; Molecular; Morbidity - disease rate; Muscle Cells; Myocardial; Myocardial Ischemia; Myocardial dysfunction; Myocardial tissue; Myocardium; National Heart, Lung, and Blood Institute; Nitrogen; Ohio; Outcome; Oxidation-Reduction; Oxygen; Pathway interactions; Physiological; Post-Translational Protein Processing; Potassium; Predisposition; Principal Investigator; Proteins; Rattus; Reactive Nitrogen Species; Reactive Oxygen Species; Reperfusion Injury; Reperfusion Therapy; Reporting; Research; Research Institute; Research Personnel; Resources; Role; Rotation; Sex Characteristics; Signal Transduction; Spectrum Analysis; Techniques; Tissues; Training; Translations; United States; Universities; Work; base; career; design; effective therapy; in vivo; insight; knowledge base; mortality; planetary Atmosphere; preconditioning; programs; response; response to injury; sex; sexual dimorphism; skills; success; tissue oxygenation; working group

SPACE PROVIDED. Cardiovascular Disease is the leading cause of morbidity and mortality in the United States. As stated above it is imperative that vve understand the mechanisms responsible for ischemic heart disease so that more effective therapies can be designed. This award will expand the Principal investigator's (PI) skills and develop his academic career in Cardiovascular Ischemia-Reperfusion Medicine by combining a career plan to supplement his knowledge base with laboratory rotations with experts in the field. The PI is a Ph.D/M.D. with advanced research and clinical training in Cardiovascular Medicine and Interventional Cardiology. Mentored by Dr. Jay Zweier, a recognized world leader in ischemia-reperfusion injury, magnetic resonance imaging techniques and oxidative biology, and Dr. Muthu Periasamy, a world leader in myocyte biology and calcium handling, and Dr. Elizabeth Murphy, a world leader in myocardial ischemia-reperfusion biology and sex-differences, the PI will perform studies using the unique resources available within Davis Heart and Lung Research Institute (DHLRI) and The Ohio State University Biomedical Spectroscopy and Imaging Center. The importance of understanding the mechanisms responsible for ischemic heart disease was highlighted by the report of the NHLBI Working Group on the Translation of Therapies for Protecting the Heart which recognized that "fundamental gaps in knowledge remain that limit the effective translation of cardioprotective therapies from experimental to clinical settings." This research program will investigate the role of the sarcolemmal ATP-sensitive potassium channel (sarc-KATp) in susceptibility to ischemia-reperfusion (l/R) injury, examining specifically the effect on calcium handling and the generation of reactive oxygen species and reactive nitrogen species using physiological, biochemical, molecular and EPR techniques that are uniquely available within the Zweier lab and The Ohio State University EPR imaging center. The specific aims are to examine the sexual dimorphisms observed with KATP channel knockout with respect to : (1) The effect of sarc-KATP channel activity on in vivo formation of reactive oxygen and nitrogen species (ROS, RNS) and tissue oxygenation during myocardial ischemia-reperfusion injury, and (2) The effect of sarc-KATP channel expression on calcium handling protein levels, activity, and S-nitrosylation in response to ischemia- reperfusion injury in vivo and ex vivo. The availability of world-class EPR-based imaging technologies at The OSU, the outstanding expertise of the Mentor and Advisory Committee, and the qualifications ofthe PI provide an excellent atmosphere for success in the program described. This research will provide critical understanding ofthe mechanisms by which sarc-KATP channels influence the susceptibility to myocardial ischemia-reperfusion injury.

空间 假如。 心血管疾病是美国发病率和死亡率的主要原因。如上所述 vve必须了解导致缺血性心脏病的机制，以便更多 可以设计有效的疗法。该奖项将扩大主要研究者（PI）的技能和 通过结合职业计划来发展他在心血管缺血再灌注医学方面的学术生涯 通过与该领域的专家进行实验室轮换来补充他的知识库。 PI是Ph.D/M.D。 通过心血管医学和介入心脏病学的高级研究和临床培训。 由Jay Zweier博士指导，他是缺血重置损伤的全球领导者，磁共振 成像技术和氧化生物学，以及Muthu Periasamy博士，Muthu Periasamy博士是肌细胞生物学和 钙处理和伊丽莎白·墨菲（Elizabeth Murphy） 性别差异，PI将使用戴维斯心脏和肺中可用的独特资源进行研究 研究所（DHLRI）和俄亥俄州立大学的生物医学光谱和成像中心。 理解负责缺血性心脏病的机制的重要性被强调 通过NHLBI工作组的报告，关于保护心脏的疗法的翻译 认识到“知识的基本差距仍然限制了心脏保护的有效翻译 从实验到临床环境的疗法。”该研究计划将研究 对缺血再灌注（L/R）易感性（sarc-katp）的肌膜ATP敏感钾通道（SARC-KATP） 损伤，特别检查对钙处理的影响和活性氧的产生 使用生理，生化，分子和EPR技术的反应性氮种是 Zweier实验室和俄亥俄州立大学EPR成像中心的独特可用。具体 目的是检查使用KATP通道敲除的性二态性相对于：（1） SARC-KATP通道活性对反应性氧和氮种的体内形成（ROS，RNS）的影响 在心肌缺血 - 再灌注损伤期间的组织氧合，以及（2）SARC-KATP的影响 钙处理蛋白水平，活性和S-亚硝基化的通道表达，响应缺血 - 体内的再灌注损伤。 OSU的世界一流基于EPR的成像技术的可用性，这是杰出的专业知识 导师和咨询委员会以及PI的资格为 所描述的程序中的成功。这项研究将对机制提供批判性理解 SARC-KATP通道会影响心肌缺血 - 再灌注损伤的敏感性。

项目成果

Role of adenosine A2B receptor signaling in contribution of cardiac mesenchymal stem-like cells to myocardial scar formation.

腺苷 A2B 受体信号传导在心脏间充质干细胞样细胞对心肌疤痕形成的贡献中的作用。

• DOI: 10.1007/s11302-014-9410-y
• 发表时间: 2014
• 期刊: Purinergic signalling
• 影响因子: 3.5
• 作者: Ryzhov,Sergey;Sung,BongHwan;Zhang,Qinkun;Weaver,Alissa;Gumina,RichardJ;Biaggioni,Italo;Feoktistov,Igor
• 通讯作者: Feoktistov,Igor

Comparison of Impella and intra-aortic balloon pump in high-risk percutaneous coronary intervention: vascular complications and incidence of bleeding.

• DOI: 10.3109/17482941.2012.741244
• 发表时间: 2012-12-01
• 期刊: Acute cardiac care
• 作者: Boudoulas, Konstantinos Dean;Pederzolli, Andrew;Pompili, Vincent J
• 通讯作者: Pompili, Vincent J

Impact of cardiac-specific expression of CD39 on myocardial infarct size in mice.

CD39 心脏特异性表达对小鼠心肌梗死面积的影响。

• DOI: 10.1016/j.lfs.2016.10.016
• 发表时间: 2017
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: Smith,StephenB;Xu,Zhaobin;Novitskaya,Tatiana;Zhang,Bo;Chepurko,Elena;Pu,Xin-An;Wheeler,DebraG;Ziolo,Mark;Gumina,RichardJ
• 通讯作者: Gumina,RichardJ