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; 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）： 该提案描述了一项为期5年的培训计划，以开发以研究为重点的心血管医学学术生涯。在激活该奖项时，首席研究人员将完成他在内科和心血管医学方面的培训，并打算将过渡成为具有必要科学专业知识的独立医师科学家。首席赞助商兼导师Keith March博士是血管重塑和血管生成领域的公认领导者，并将协助首席研究人员在奖励期内实现其科学和职业发展目标。除赞助商外，咨询委员会还包括在血管信号传导，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，还将在整个资金期间提供科学的指导和职业发展建议。印第安纳大学的出色研究环境，尤其是印第安纳州血管生物学和医学中心的综合性质，似乎是成为独立医师科学家的职业发展的理想选择。该项目将集中于理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率和死亡率的主要原因。高水平的活性氧（ROS）对血管内皮的损害称为“氧化应激”，似乎是促进动脉粥样硬化的一种机制。另一方面，低水平的ROS似乎是生理的，可能会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体。我们的初步数据表明，EPC对过氧化氢以及同型半胱氨酸产生的ROS敏感，但尚不清楚哪种机制介导了EPC中的效果或ROS如何详细影响EPC的功能。需要这种知识来了解ROS在脉管系统中的生理和病理生理作用。因此，我们将首先研究ROS对特定目标中EPC的存活，分化和成熟的影响。然后，我们将通过研究ARS在AIM 2中调节EPC的体外和体内的功能来补充这一点。