Mentoring in cholinergic regulation of vascular oxidation

血管氧化的胆碱能调节的指导

基本信息

批准号：
10664768
负责人：
Cyndya Adriana Shibao
金额：
$ 11.6万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-20 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10664768
关键词：
3-nitrotyrosine Academia Academic Medical Centers Acetylcholinesterase Acetylcholinesterase Inhibitors Acute African African American population Animal Model Antigen-Presenting Cells Aorta Area Atherosclerosis Award Blinded Blood Vessels Cardiovascular Diseases Cause of Death Chronic Clinical Pharmacology Collaborations Credentialing Dedications Development Ear lobe Endothelial Cells Endothelium Enrollment Event Faculty Foundations Functional disorder Funding Galantamine Harvest Hispanic Populations Hypertension Impairment Inflammation Inflammation Mediators Inflammatory Infusion procedures Intercellular adhesion molecule 1 Intervention Leadership Link Lipids Measures Mediating Medicine Mentors Morbidity - disease rate NADP NADPH Oxidase Nitric Oxide Nitric Oxide Signaling Pathway Outcome Oxidative Stress Parasympathetic Nervous System Parents Participant Peripheral Blood Mononuclear Cell Population Postdoctoral Fellow Production Proteins Publications Reactive Oxygen Species Regulation Research Research Personnel Research Project Grants Research Training Signal Pathway Source Strategic Planning Superoxides Testing Time Tragus Training Work adduct bioelectronics career cholinergic cytokine effective therapy endothelial dysfunction experience immune activation immunogenic improved inflammatory marker member mid-career faculty monocyte mortality neuroregulation novel novel strategies oxidation patient oriented prevent randomized placebo controlled study response skills training opportunity transmission process vagus nerve stimulation vascular endothelial dysfunction vascular inflammation

3-nitrotyrosine Academia Academic Medical Centers Acetylcholinesterase Acetylcholinesterase Inhibitors Acute African African American population Animal Model Antigen-Presenting Cells Aorta Area Atherosclerosis Award Blinded Blood Vessels Cardiovascular Diseases Cause of Death Chronic Clinical Pharmacology Collaborations Credentialing Dedications Development Ear lobe Endothelial Cells Endothelium Enrollment Event Faculty Foundations Functional disorder Funding Galantamine Harvest Hispanic Populations Hypertension Impairment Inflammation Inflammation Mediators Inflammatory Infusion procedures Intercellular adhesion molecule 1 Intervention Leadership Link Lipids Measures Mediating Medicine Mentors Morbidity - disease rate NADP NADPH Oxidase Nitric Oxide Nitric Oxide Signaling Pathway Outcome Oxidative Stress Parasympathetic Nervous System Parents Participant Peripheral Blood Mononuclear Cell Population Postdoctoral Fellow Production Proteins Publications Reactive Oxygen Species Regulation Research Research Personnel Research Project Grants Research Training Signal Pathway Source Strategic Planning Superoxides Testing Time Tragus Training Work adduct bioelectronics career cholinergic cytokine effective therapy endothelial dysfunction experience immune activation immunogenic improved inflammatory marker member mid-career faculty monocyte mortality neuroregulation novel novel strategies oxidation patient oriented prevent randomized placebo controlled study response skills training opportunity transmission process vagus nerve stimulation vascular endothelial dysfunction vascular inflammation

展开

项目摘要

PROJECT SUMMARY/ABSTRACT This K24 proposal will provide protected time for Dr. Cyndya Shibao to deliver high-quality mentoring to post-doctoral and junior faculty investigators at Vanderbilt University Medical Center. In this regard, she proposes a comprehensive and dedicated mentoring plan that will facilitate the effective transition of her mentees into independent academic careers. Her application includes an across-the-board strategy to augment her training through acquisition of advanced skills in mentoring, training in diversity, leadership, and strategic planning. In addition, her research plan includes a cross-collaboration with members of the Feinstein Institute of Bioelectronic Medicine to acquire additional expertise in vagus nerve stimulation, which is thematically link to her current studies on parasympathetic cholinergic regulation of vascular oxidation. Endothelial dysfunction, a pro-thrombotic, inflammatory condition that causes impaired vascular reactivity is an early reversible step in the development of atherosclerosis and cardiovascular disease (CVD). Multiple studies consistently shown that African Americans (AAs) have impaired endothelial function compared to whites. African Americans also experience disproportionately higher CV morbidity and 20% higher mortality than whites or Hispanics. Endothelial dysfunction is caused by the overproduction of reactive oxygen species (ROS), particularly superoxide which interferes with endothelial-derived nitric oxide signaling pathways. One of the major sources of superoxide is NADPH oxidase; our previous work found that activation of NADPH oxidase contributes to vascular oxidation through immune cell activation. It is well-known that inflammation and oxidative stress are modulated by the parasympathetic nervous system (PNS). Dr. Shibao and others found that AAs have reduced PNS activity compared with whites. Currently, her funded studies are focused on the effect of central acetylcholinesterase inhibition, which increases cholinergic activity, on vascular oxidative stress in this population. For this K24 application, she will expand these studies to determine if trans- auricular vagus nerve stimulation (TaVNS), another intervention that stimulates PNS, prevents immune cell activation, reduces markers of vascular oxidation in harvested endothelial cells and improve endothelial function as measured by flow-mediated dilation. The planned studies will provide a comprehensive assessment of the mechanism underlying the effect of increased PNS transmission on vascular oxidation and inflammation, which precedes endothelial dysfunction in African Americnas. Furthermore, these studies will provide ample training opportunities for Dr. Shibao’s mentees in the area of cholinergic regulation of vascular oxidation.

项目摘要/摘要该K24提案将为Cyndya Shibao博士提供受保护的时间，以提供高质量的指导范德比尔特大学医学中心的博士后和初级教师调查员。在这方面，她提案一项全面而敬业的心理计划，将有助于她的有效过渡梅纳（Menees）从事独立的学术职业。她的申请包括一个全面策略通过获得精神，多样性，领导力培训的高级技能来增加培训战略计划。此外，她的研究计划还包括与Feinstein成员的交叉合作生物电子医学研究所，以获得迷走神经刺激方面的其他专业知识，主题与她目前关于血管氧化副交感神经能调节的研究有关。内皮功能障碍是导致血管反应受损的促栓性的炎症状况动脉粥样硬化和心血管疾病（CVD）发展的早期可逆步骤。多种的研究始终表明，非洲裔美国人（AAS）与白人。非洲裔美国人也经历了更高的CV发病率，死亡率更高20％比白人或西班牙裔。内皮功能障碍是由活性氧的生产过多引起的（ROS），尤其是超氧化物，干扰了内皮衍生的一氧化氮信号通路。之一超氧化物的主要来源是NADPH氧化酶。我们以前的工作发现NADPH氧化酶的激活通过免疫细胞激活有助于血管氧化。众所周知，注射和氧化应激由副交感神经系统（PNS）调节。 Shibao博士等发现与白人相比，AAS的PNS活性降低。目前，她资助的研究是侧重于中央乙酰胆碱酯酶抑制作用，从而增加胆碱能活性对血管该人群中的氧化应激。对于此K24的应用，她将扩展这些研究，以确定是否跨耳神经刺激（TAVNS）是刺激PNS的另一种干预措施，可防止免疫细胞激活，减少收获的内皮细胞中血管氧化的标志物并改善内皮通过流介导的字典测量的功能。计划的研究将提供全面的评估增加PNS传播对血管氧化和血管氧化作用的影响的机制炎症，在非裔美国人NAS的内皮功能障碍之前。此外，这些研究将在血管胆碱能调节的领域，为Shibao博士的Menees提供了充足的培训机会氧化。