Reactive Oxygen Species on Endothelial Progenitor Cells

内皮祖细胞上的活性氧

• 批准号: 7079710
• 负责人: Jalees Rehman
• 金额: $ 13.3万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7079710
• 关键词: angiogenesis; antioxidants; apoptosis; atherosclerosis; athymic mouse; biological signal transduction; cell differentiation; cell growth regulation; cell proliferation; clinical research; free radical oxygen; growth factor; homocysteine; human tissue; hydrogen peroxide; hypoxia; ischemia; mitogen activated protein kinase; monocyte; nuclear factor kappa beta; oxidative stress; pathologic process; stem cell transplantation; stem cells; vascular endothelium

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of a research focused academic career in cardiovascular medicine. The principal investigator will have completed his training in internal medicine and cardiovascular medicine at the time of the activation of this award and intends to make the transition into becoming an independent physician scientist with the necessary scientific expertise. The chief sponsor and mentor, Dr. Keith March, is a recognized leader in the field of vascular remodeling and angiogenesis and will assist the principal investigator to accomplish his scientific and career development goals during the award period. In addition to his sponsor, an advisory committee, consisting of leading experts in the areas of vascular signaling, reactive oxygen species and progenitor cell biology, will provide scientific guidance and career development advice throughout the funding period. The excellent research environment at Indiana University and especially the integrative nature of the Indiana Center for Vascular Biology and Medicine appear to be ideal for the career development into an independent physician scientist. This project will focus on understanding the role of reactive oxygen species in modulating the function of endothelial progenitor cells. Atherosclerosis is a major cause of morbidity and mortality. Damage to the vascular endothelium by high levels of reactive oxygen species (ROS) is referred to "oxidative stress" and appears to be one mechanism promoting atherosclerosis. Low levels of ROS on the other hand appear to be physiologic and may mediate necessary vascular responses. Endothelial progenitor cells (EPCs) have recently been identified as key mediators in vasculoprotective processes like angiogenesis and vascular regeneration. Our preliminary data demonstrates that EPCs are sensitive to ROS generated by hydrogen peroxide as well as homocysteine, but it is not known which mechanisms mediate the effects in EPCs or how ROS affect the function of EPCs in detail. This knowledge is required to understand the physiologic and pathophysiologic role of ROS in the vasculature. We will therefore first study the effects of ROS on the survival, differentiation and maturation of EPCs in Specific Aim 1. We will then complement this by examining how ROS can modulate the functions of EPCs in vitro and in vivo in Aim 2. Finally, we will identify potential signal transduction pathways mediating the ROS effects on endothelial progenitor cells in Aim 3.

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，旨在发展心血管医学领域的研究型学术生涯。在该奖项启动时，主要研究者将完成内科和心血管医学的培训，并打算转型成为一名具有必要科学专业知识的独立医师科学家。首席发起人和导师Keith March博士是血管重塑和血管生成领域公认的领导者，他将在奖励期间协助首席研究员完成其科学和职业发展目标。除了他的赞助商之外，一个由血管信号、活性氧和祖细胞生物学领域的领先专家组成的咨询委员会将在整个资助期间提供科学指导和职业发展建议。印第安纳大学优良的研究环境，特别是印第安纳血管生物学和医学中心的综合性似乎是独立医师科学家职业发展的理想选择。该项目将重点了解活性氧在调节内皮祖细胞功能中的作用。动脉粥样硬化是发病和死亡的主要原因。高水平的活性氧（ROS）对血管内皮的损伤被称为“氧化应激”，并且似乎是促进动脉粥样硬化的一种机制。另一方面，低水平的活性氧似乎是生理性的，可能介导必要的血管反应。内皮祖细胞（EPC）最近被确定为血管生成和血管再生等血管保护过程中的关键介质。我们的初步数据表明EPCs对过氧化氢和同型半胱氨酸产生的ROS敏感，但尚不清楚哪些机制介导EPCs的作用或ROS如何详细影响EPCs的功能。了解 ROS 在脉管系统中的生理和病理生理作用需要这些知识。因此，我们将首先在具体目标 1 中研究 ROS 对 EPC 存活、分化和成熟的影响。然后，我们将在目标 2 中通过研究 ROS 如何在体外和体内调节 EPC 的功能来补充这一点。最后，我们将在目标 3 中确定介导 ROS 对内皮祖细胞影响的潜在信号转导途径。