Autonomic and Vascular Mechanisms of Cardiovascular Risk in Women with Post-traumatic Stress Disorder (PTSD)

项目摘要 K 01提案的最终目标是使Ida Fonkoue博士成为一名独立的研究人员， 研究人员通过1）发展人类血管，激素和睡眠测量方面的专业知识; 2）获得 通过严格的培训计划，在一个优秀的科学环境中， 转化血管研究的传统; 3）产生足够的初步结果，以支持NIH R 01应用程序。候选人的长期目标是建立一个NIH资助的临床研究项目， 妇女健康的转化研究，研究血管、神经和激素控制的紊乱， 导致患有慢性高血压和心血管疾病（CVD）的女性的高发病率 压力暴露，如创伤后应激障碍（PTSD）、广泛性焦虑症或 恐慌症 超过700万美国成年人患有PTSD，这是一种与高血压风险相关的疾病， CVD。虽然健康的绝经前女性相对于男性受到CVD的保护，但诊断 创伤后应激障碍的发生会使女性心血管疾病的风险增加3倍。了解CVD风险的潜在机制 患有创伤后应激障碍的妇女制定旨在保护未来的干预策略至关重要 这些弱势群体的健康。根据我们的初步数据，该项目的工作假设是 PTSD抑制了一氧化氮的生物利用度，导致内皮功能下降，动脉粥样硬化程度增加， 僵硬和交感神经激活增加;这些变化因雌二醇水平低而加剧 和睡眠障碍目的1将确定绝经前PTSD妇女SNS活性的改变， 确定这些变化是否是低E2水平和睡眠障碍的函数。目标2将识别 患有创伤后应激障碍的绝经前女性血管功能的变化，并确定这些变化是否是一种 低E2水平和睡眠障碍的功能。 埃默里大学，PI的整个指导团队所在地，拥有丰富的学术研究 环境，其资源将用于开展拟议的研究，包括NIH资助的 格鲁吉亚临床和转化科学联盟（GA CTSA）。在K 01授予期间，PI将投入75% 她在四年的培训中强调了对该项目和职业发展相关活动的努力， 研究计划。她将完成由GA CTSA提供的临床研究理学硕士学位， 准备未来职业发展补助金的提交。该研究项目结合多学科 导师，教学教育和实践经验，将为Fonkoue博士提供培训和技能， 成为一名成功的独立调查员。

PROJECT SUMMARY The ultimate objective of this K01 proposal is to enable Dr. Ida Fonkoue to become an independent research investigator by 1) developing expertise in vascular, hormonal and sleep measures in humans; 2) acquiring scientific growth through a rigorous training plan, within an outstanding scientific environment that has a long tradition in translational vascular research; and 3) generating sufficient preliminary results to support an NIH R01 application. The candidate’s long-term goal is to build an NIH-funded research program in clinical and translational research in women’s health, studying derangements of vascular, neural and hormonal control, that contribute to the high rates of hypertension and cardiovascular disease (CVD) in women living with chronic stress exposure such as those with post-traumatic stress disorder (PTSD), generalized anxiety disorder or panic disorder. Over 7 million U.S. adults have PTSD, a disorder associated with a greater risk for hypertension and CVD. While healthy premenopausal women are relatively protected from CVD compared to men, a diagnosis of PTSD increases CVD risk in women by up to 3-fold. Understanding the mechanisms underlying CVD risk in women with PTSD is of paramount importance to develop intervention strategies aiming at protecting the future health of this vulnerable population. Based on our preliminary data, the working hypothesis of this project is that: PTSD inhibits nitric oxide bioavailability, resulting in decreased endothelial function, increased arterial stiffness and increased sympathetic activation; and that these changes are exacerbated by low estradiol levels and sleep disturbances. Aim 1 will identify alterations in SNS activity in premenopausal women with PTSD and determine if these alterations are a function of low E2 levels and sleep disturbances. Aim 2 will Identify alterations in vascular function in premenopausal women with PTSD and determine if these alterations are a function of low E2 levels and sleep disturbances. Emory University, where the PI’s entire mentoring team is located, boasts an intellectually rich research environment whose resources will be used to carry out the proposed research, including an NIH-funded Georgia Clinical and Translational Science Alliance (GA CTSA). During this K01 award, the PI will devote 75% effort to this project and career development-related activities as highlighted in her four years training and research plans. She will complete a Master of Science in Clinical Research offered by the GA CTSA and prepare future career development grant submission. This research project, combined with multidisciplinary mentorship, didactic education, and practical experience, will provide Dr. Fonkoue with the training and skills to become a successful independent investigator.