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

项目总结 K01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：1)开发人类血管、荷尔蒙和睡眠测量方面的专业知识；2)获得 通过严格的培训计划实现科学成长，在具有长期 翻译血管研究的传统；以及3)产生足够的初步结果来支持NIH R01应用程序。候选人的长期目标是建立一个由美国国立卫生研究院资助的临床和 女性健康中的转化性研究，研究血管、神经和激素控制的紊乱， 导致慢性阻塞性肺病患者高血压和心血管疾病(CVD)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创伤后应激障碍，这是一种与高血压和 心血管疾病。尽管与男性相比，健康的绝经前女性相对不会患心血管疾病，但一项诊断显示 创伤后应激障碍会使女性患心血管疾病的风险增加3倍。了解心血管疾病风险的潜在机制 患有创伤后应激障碍的妇女对于制定旨在保护未来的干预策略至关重要 这一弱势群体的健康。根据我们的初步数据，这个项目的工作假设是 即：创伤后应激障碍抑制一氧化氮的生物利用度，导致内皮功能下降，动脉增粗 僵硬和交感神经激活增加；低雌二醇水平加剧了这些变化 以及睡眠障碍。目标1将确定患有创伤后应激障碍的绝经前妇女SNS活性的变化 确定这些变化是否是低E2水平和睡眠障碍的结果。目标2将确定 绝经前创伤后应激障碍妇女血管功能的改变并确定这些改变是否为 低E_2水平和睡眠障碍的作用。 PI的整个指导团队所在的埃默里大学拥有丰富的智力研究 其资源将用于开展拟议研究的环境，包括由美国国立卫生研究院资助的 佐治亚州临床和转化科学联盟(GA CTSA)。在这个K01奖项中，PI将致力于75% 她在四年的培训和培训中强调了对这个项目和与职业发展相关的活动的努力 研究计划。她将完成GA CTSA提供的临床研究理学硕士学位，并 准备未来的职业发展拨款申请。本研究项目，结合多学科 指导、教育和实践经验将为丰库博士提供培训和技能，以 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.