Nitric Oxide/cGMP/Endotoxin-Induced Myocardial Dysfunct

一氧化氮/cGMP/内毒素引起的心肌功能障碍

基本信息

批准号：
7226252
负责人：
FUMITO ICHINOSE
金额：
$ 13.07万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-01 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7226252
关键词：
Advisory Committees Anesthesia Department, Hospital Area Award Calcium Cardiac Cardiac Myocytes Cardiac Surgery procedures Cardiopulmonary Bypass Cardiovascular system Complement Cyclic GMP Cyclic GMP-Dependent Protein Kinases Development Endotoxemia Endotoxins Environment Enzymes Faculty Foundations Functional disorder Gene Transfer General Hospitals Impairment In Vitro Incidence Inflammation Inflammatory Knowledge Lead Massachusetts Mediator of activation protein Mentors Metabolism Molecular Molecular and Cellular Biology Morbidity - disease rate Mus Muscle Cells Myocardial Myocardial Infarction Myocardial dysfunction NOS2A gene Nitric Oxide Pathogenesis Personal Satisfaction Physicians Physiology Postdoctoral Fellow Principal Investigator Process Production Program Development Protein Overexpression Reporting Research Research Personnel Research Training Role Saline Scientist Sepsis Signal Transduction Students Training Training Programs Transgenic Mice Ventricular Remodeling base career cytokine experience human NOS2A protein in vivo insight medical schools member mortality programs research study restoration skills sudden cardiac death

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of an independent investigator in the area of NO/cGMP signaling and myocardial dysfunction. The principal investigator is a junior member of the faculty in the Department of Anesthesia at the Harvard Medical School with a background in physiology, who now will acquire new knowledge and skills in molecular and cellular biology to advance his academic career. This proposal will focus on the role of NO/cGMP signaling in myocardial dysfunction associated with systemic inflammation. Kenneth D. Bloch, MD, will mentor the principal investigator's scientific development. Dr. Bloch is a recognized expert in the field of NO/cGMP signaling and has extensive experience in training postdoctoral fellows and graduate students. To complement Dr. Bloch's expertise, the training program enlists the expertise of Roger J. Hajjar, MD, as a co-sponsor, who is an expert in myocardial cellular and molecular biology, as well as cardiac gene transfer. In addition, an advisory committee of highly respected physician scientists will provide scientific and career advice. The proposed experiments will examine the role of NOS2, cGMP and cGMP-dependent protein kinase (PKG) in the myocardial dysfunction associated with endotoxemia. Specifically, the applicant proposes to assess whether NOS2 is sufficient or required, but not sufficient, to cause endotoxin-induced myocardial dysfunction. In addition, the contribution of increased myocardial cGMP concentrations and PKG activation to the myocardial dysfunction associated with systemic inflammation will be examined. Studies will be performed on isolated cardiomyocytes, as well as in vivo using transgenic mice and mice subjected to cardiac gene transfer. Together, the proposed studies will illuminate the role of NOS2 and cGMP-dependent signaling in the pathogenesis of myocardial dysfunction associated with systemic inflammation. This award will permit the applicant to take advantage of the outstanding research training environment of the Cardiovascular Research Center of the Massachusetts General Hospital for the acquisition of new knowledge and skills in cell and molecular biology. In addition, a carefully constructed training program has been developed that will permit successful development of an independent research career examining the basic mechanisms of myocardial dysfunction associated with systemic inflammation.

描述（由申请人提供）：该提案描述了一个为期 5 年的培训计划，旨在培养 NO/cGMP 信号传导和心肌功能障碍领域的独立研究者。首席研究员是哈佛医学院麻醉系的一名初级教师，具有生理学背景，他现在将获得分子和细胞生物学的新知识和技能，以推进他的学术生涯。该提案将重点关注 NO/cGMP 信号在与全身炎症相关的心肌功能障碍中的作用。医学博士 Kenneth D. Bloch 将指导首席研究员的科学发展。 Bloch 博士是 NO/cGMP 信号传导领域公认的专家，在培养博士后和研究生方面拥有丰富的经验。为了补充 Bloch 博士的专业知识，该培训计划邀请了医学博士 Roger J. Hajjar 的专业知识作为共同发起人，他是心肌细胞和分子生物学以及心脏基因转移方面的专家。此外，由备受尊敬的医学科学家组成的咨询委员会将提供科学和职业建议。拟议的实验将检查 NOS2、cGMP 和 cGMP 依赖性蛋白激酶 (PKG) 在与内毒素血症相关的心肌功能障碍中的作用。具体地，申请人建议评估NOS2是否足以或需要但不足以引起内毒素诱导的心肌功能障碍。此外，还将检查心肌 cGMP 浓度增加和 PKG 激活对与全身炎症相关的心肌功能障碍的影响。将对分离的心肌细胞以及转基因小鼠和接受心脏基因转移的小鼠进行体内研究。总之，拟议的研究将阐明 NOS2 和 cGMP 依赖性信号传导在与全身炎症相关的心肌功能障碍的发病机制中的作用。该奖项将使申请人能够利用马萨诸塞州总医院心血管研究中心出色的研究培训环境来获取细胞和分子生物学方面的新知识和技能。此外，还制定了精心构建的培训计划，该计划将允许成功发展独立研究事业，检查与全身炎症相关的心肌功能障碍的基本机制。