Equol Supplementation for Improving Vascular Function in Postmenopausal Women with CKD: Efficacy and Mechanistic Role of GPER - PROJECT SUMMARY/ABSTRACT CANDIDATE: Ester Oh, Ph.D., is an instructor, who recently completed her postdoctoral fellowship, in the Division of Renal Diseases and Hypertension at the University of Colorado Anschutz Medical Campus. She has an impressive record of productivity, including prior pre- and post-doctoral grant funding and a strong publication history. Dr. Oh’s ultimate career goal is to independently direct a laboratory focused on evaluating new, evidence- based, pharmacological interventions to improve vascular function and delineate the underlying sex-specific mechanisms in populations at high risk of cardiovascular disease (CVD), including chronic kidney disease (CKD). CAREER DEVELOPMENT PLAN: Dr. Oh’s proposed training plan will address key deficiencies in her training to date and allow her to accomplish her career goal of becoming a successful independent investigator. Dr. Oh’s training plan will consist of: 1) acquiring research skills to conduct fully independent clinical and animal studies; 2) new research skills associated with the proposed research that will distinguish Dr. Oh’s work from those of her mentors and develop her independent line of research; and 3) intellectual and professional skills development through coursework, attendance/presentations at journal clubs, seminars, and national scientific meetings, more grant writing and mentoring experience, and regular interactions with her advisory team. ENVIRONMENT: The environment for Dr. Oh’s training plan will be outstanding. The primary mentor Dr. Nowak (clinical vascular physiology in CKD) and co-mentor Dr. Brunt (translational cardiovascular physiology utilizing both clinical and pre-clinical approach) have been continuously funded by NIH and have strong records of successful mentoring in translational biomedical research. Dr. Oh’s mentorship team also includes two advisory team members Dr. Moreau (sex differences and effects of menopause on cardiovascular physiology) and Dr. Lindsey (G protein-coupled estrogen receptor [GPER] signaling mechanisms). RESEARCH: CVD is a major cause of death in patients with CKD, which is largely attributable to the development of vascular dysfunction primarily vascular endothelial dysfunction and large elastic artery stiffening. In women, there is a greater prevalence of CKD and a faster rate of decline in CKD-associated blood vessel function than in men. However, research on women with CKD is especially lacking. Despite its beneficial effect on the vasculature, long-term use of estrogen-based hormone therapy has raised concerns due to its potential adverse effects. Thus, it is necessary to identify alternative, safe compounds to hormone therapy that can improve vascular function in women with CKD at high CVD risk. One such alternative is equol, a gut-derived metabolite of soy isoflavone daidzein. Equol is a unique phytoestrogen that can activate GPER, which is prevalent in the vascular endothelium and a potential therapeutic target for improving vascular health. The proposed research will test the efficacy of oral equol supplementation for improving vascular function in postmenopausal women with CKD (Aim 1&2A) and examine the mechanistic role of GPER for equol-induced vascular improvements in animal models (Aim 2B).
