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.

PROJECT NARRATIVE The prevalence of post-traumatic stress disorder (PTSD) is growing at an alarming rate in the U.S, and these patients are at significantly greater risk for developing hypertension and cardiovascular disease. Women are twice as likely as men to develop PTSD, a chronic stress disorder that may negate the cardiovascular protection conferred by female hormones before menopause. This study of the neural and vascular consequences of PTSD in premenopausal women will help inform the development of therapies to improve cardiovascular health in this growing and high-risk population of women.