The applicant's long-term career goal is to become an independent nurse scientist with expertise in biobehavioral research related to cardiovascular health. A K23 award will provide her with the training and support necessary to accomplish the following goals: (1) expand knowledge of vascular biology; (2) increase research method capacities to measure cardiovascular function; (3) advance laboratory techniques for genetics research and acquire the knowledge and skills needed for genomics data analysis; and (4) develop a laboratory procedure to reliably induce stress in human research subjects. To achieve these goals, the applicant has assembled an interdisciplinary mentoring committee comprised of a primary mentor, Dr. Brian Annex, an internationally recognized clinical researcher in arterial diseases, and four co-mentors: Drs. Eugene Barrett and Zhenqi Liu, experts in quantifying arterial stiffness and vascular function; Dr. Charles Farber, a geneticist who has extensive experience in RNA-sequencing and genomics analysis; and Dr. Bethany Teachman, a well-known psychologist who will train the applicant on the Trier Social Stress Test. Arterial stiffness is an independent predictor of hypertension. The applicant's previous study conducted during her NRSA fellowship revealed that chronic psychological stress was a significant predictor of arterial stiffness in nonhypertensive people, independent of age and blood pressure. As a next step, she will examine how (Aims 1 and 3 below) and whether (Aim 2 below) psychological stress causes arterial stiffness in the context of chronic and acute stress. The proposed study will use a randomized, controlled design with a sample of 80 female Caucasians aged 30-55 years old. Genomic methodologies will be incorporated into this research to provide a global picture of cardiovascular responses to stress. The study aims are (1) to examine whether chronic stress predicts arterial stiffness through the mediational effects of increased sympathetic activity, decreased parasympathetic activity, increased matrix metalloproteinase (MMP) 2 & 9, and decreased nitric oxide (NO)-bioavailability; (2) to examine if acute stress, induced by the Trier Social Stress Test (TSST), causes increased sympathetic activity, decreased parasympathetic activity, increased MMP 2&9, decreased NO-bioavailability, and increased arterial stiffness; and (3) to identify genes whose expression is associated with each measure of chronic stress, sympathetic activity, parasympathetic activity, MMP 2&9, NO- bioavailability, and arterial stiffness. The study results will increase knowledge regarding causal effects of psychological stress on arterial stiffness and its underlying mechanisms, and also provide foundational information for future work on developing preventive interventions to reduce arterial stiffness through identified mechanisms.
Arterial stiffness is an important subclinical condition of cardiovascular disease, which is the number one killer in the United States. The knowledge obtained from this study will provide a better understanding of causal effects of psychological stress on arterial stiffness and will inform future studies to develop and evaluate strategies for prevention and treatment of excessive arterial stiffness.