Vascular Biology: Aging and Endothelial Dysfunction

总体描述：(来自应用程序)此应用程序适用于一位导师 研究科学家发展奖旨在提供这一原则 接受过衰老生物学和生理方面额外培训的调查员 无所事事。申请人：申请人的主要研究领域是 血管生物学。申请者的直接目标是获得额外的 分子生物学方面的培训。申请者的长期目标是 发展一项专注于分子机制的独立研究计划 衰老和缺乏体力活动对血管的有害影响 功能。此外，其有益效果的分子基础 运动训练改善年龄和缺乏体力活动的影响 将会被研究。 职业发展/培训计划：本建议书的培训计划包括 两个主要要素：1.)分子科学新技能的获得 可应用于生理学研究的生物学，以及2.结构化 活动包括研究道德方面的正式培训；参与 期刊俱乐部和系列研讨会；在科学会议上发表演讲；以及 每周，与申请者的赞助人举行辅导会议。研究计划： 此次调查旨在确定责任机制(S) 与衰老相关的内皮功能障碍。特别强调的是 被放在测试关于内皮一氧化氮的作用的假说上 一氧化氮合酶在青年和老年大鼠血管反应性调节中的作用。 一般的假设是内皮功能障碍与衰老有关 而缺乏运动是由于eNOS基因表达下调所致 骨骼肌动脉网中的血管内皮细胞。这个 本申请的具体目的是：1.)确定机制 衰老时内皮介导的血管反应受损的原因 大鼠，2.)确定内皮型一氧化氮合酶基因的流动/剪应力调节机制 在衰老大鼠动脉和小动脉中的表达，3。确定是否 血管内皮型一氧化氮合酶的过度表达将增强血管内皮细胞功能 衰老大鼠和4)。确定运动训练的效果 诱导eNOS基因表达增强衰老大鼠血管内皮细胞功能 老鼠。环境：拟议的研究将在道尔顿酒店进行 心血管研究中心和兽医生物医学系 密苏里大学的理科专业。赞助商M·哈罗德·劳克林 博士，是血管领域的知名研究员和导师 运动生理学。共同发起人埃尔默·M·普莱斯博士是一位知名的 分子生物学领域的研究人员。咨询导师唐纳德 D.Heistad，医学博士，是血管分子领域公认的专家 生物学。

OVERALL DESCRIPTION: (from the application) This application for a Mentored Research Scientist Development Award is designed to provide the principle investigator with additional training in the biology of aging and physical inactivity. Applicant: The applicant's primary area of research interest is vascular biology. The immediate goal of the applicant is to gain additional training in molecular biology. The long-term goal of the applicant is to develop an independent research program focusing on the molecular mechanisms for the detrimental effects of aging and physical inactivity on vascular function. In addition, the molecular basis for the beneficial effects of exercise training in ameliorating the effects of age and physical inactivity will be studied. Career Development/Traininq Plan: The training plan of this proposal consists of two primary elements: 1.) the acquisition of new skills in molecular biology that can be applied to physiological studies, and 2.) structured activities including formal training in research ethics; participation in journal clubs and seminar series; presentations at scientific meetings; and weekly, mentoring sessions with the applicant's sponsor. Research Plan: The purpose of this investigation is to determine the mechanism(s) responsible for the endothelial dysfunction associated with aging. Particular emphasis will be placed on testing hypotheses concerning the role of endothelial nitric oxide synthase (eNOS) in regulating vascular reactivity in young and old rats. The general hypothesis is that endothelial dysfunction associated with aging and physical inactivity is due to a down-regulation of eNOS gene expression in vascular endothelium throughout the arterial network in skeletal muscle. The specific aims of this application are to: 1.) Determine the mechanisms responsible for impaired endothelium mediated vascular responses in senescent rats, 2.) Determine the mechanism of flow/shear stress regulation of eNOS gene expression in arteries and arterioles of senescent rats, 3.) Determine whether over expression of eNOS in blood vessels will enhance endothelial function in senescent rats, and 4.) Determine the efficacy of exercise training in inducing eNOS gene expression and enhancing endothelial function in senescent rats. Environment: The proposed studies will be conducted at the Dalton Cardiovascular Research Center and the Department of Veterinary Biomedical Sciences at the University of Missouri. The sponsor, M. Harold Laughlin, Ph.D., is an established investigator and mentor in the field of vascular exercise physiology. The Co-Sponsor, Elmer M. Price, Ph.D., is an established investigator in the field of molecular biology. The consulting mentor, Donald D. Heistad, M.D., is a recognized expert in the field of vascular molecular biology.