Vascular Biology: Aging and Endothelial Dysfunction

总体描述：（来自应用程序）此应用程序的辅导 研究科学家发展奖旨在提供原则 研究人员在生物学的老化和物理 不活动。申请人：申请人的主要研究领域是 血管生物学申请人的直接目标是获得额外的 接受过分子生物学方面的培训申请人的长期目标是 发展一个独立的研究计划，专注于分子机制 衰老和缺乏体力活动对血管的有害影响 功能 此外，对有益效果的分子基础 运动训练可改善年龄和身体活动不足的影响 将被研究。 职业发展/培训计划：本提案的培训计划包括 两个基本要素：1）。获得分子生物学方面的新技能 可以应用于生理学研究的生物学，以及2.）结构化 包括研究伦理方面的正式培训; 期刊俱乐部和系列研讨会;在科学会议上发表演讲;以及 每周与申请人的担保人进行辅导。研究计划：The 本次调查的目的是确定负责 与衰老相关的内皮功能障碍。将特别强调 被放置在测试假设有关的作用内皮一氧化氮 一氧化氮合酶（eNOS）在调节血管反应性中的作用。 一般的假设是，内皮功能障碍与衰老有关， 缺乏体力活动是由于eNOS基因表达下调， 骨骼肌中贯穿动脉网络的血管内皮。的 本申请的具体目的是：1.）确定机制 负责衰老中内皮介导的血管反应受损 大鼠，2.）确定eNOS基因的流动/切应力调节机制 在衰老大鼠的动脉和小动脉中的表达，3.）确定是否 内皮型一氧化氮合酶在血管中的过度表达将增强内皮功能， 衰老大鼠，和4.）确定运动训练的有效性， 诱导内皮型一氧化氮合酶基因表达增强内皮功能 大鼠环境：拟定研究将在道尔顿进行 心血管研究中心和兽医生物医学系 在密苏里州大学的科学。赞助商，M。哈罗德·劳克林 哲学博士、是血管领域的资深研究者和导师， 运动生理学联合赞助商Elmer M.普莱斯博士，是一个既定 分子生物学领域的研究者。咨询顾问唐纳德 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.