Psychosocial stress is increasingly recognized as an important modifiable risk factor for CVD, which could be better targeted for preventative interventions. A common behavior under stress is stress-eating, or excessive intake of high fat/sugar foods, which additionally contributes to CVD risk. Chronic stress and stress-eating may interfere with key mechanisms of endothelial repair and regeneration, setting individuals on a trajectory of accelerated development of atherosclerosis. Endothelial progenitor cell (EPC) number and function are excellent candidate biomarker outcomes for preventative intervention studies. EPCs contribute to vascular endothelial regeneration, correlate highly with frank endothelial dysfunction and atherosclerotic plaque development, and predict the development of CVD among healthy individuals. This proposed project will test two crucial and non-exclusive pathways to evaluate whether and how stress promotes EPC impairment: 1) direct effects through physiological stress arousal, and 2) indirect effects mediated by stress-eating, which promotes a biochemical milieu likely to impair EPCs. EPC number will be quantified using multicolor flow cytometry, while EPC function will be quantified with in vitro tests such as migration capacity. Stress-EPC relationships will be tested cross-sectionally (at baseline) and following an empirically validated stress- management intervention (6 months post-baseline). To conduct this proposed project, I will gain training in: 1) randomized controlled trials, 2) flow cytometry assessment of EPCs, 3) in vitro assays of EPC functional activity, and 4) advanced biostatistical techniques that permit quantification of daily fluctuations in stress-eating relationships over a period of several weeks. I have a team of mentors and advisors who are committed to facilitating my training in these areas, and I have designed a detailed training plan that includes tutorials, hands-on work, academic coursework, and relevant seminars. I plan to use this data to obtain an R01 study to improve stress-management interventions to prevent CVD, using EPC activity as the primary outcome. These findings will provide a new understanding of this important pathway to cardiovascular health, and may lead to novel psychological or pharmacological interventions to help chronically stressed individuals reduce their CVD risk.

Public Health Relevance

This research investigates whether psychosocial stress impairs the function of cells that help regenerate blood vessel linings and protect against cardiovascular disease. In addition, this study explores whether preventative stress-management interventions can protect against stress-related declines in regenerative mechanisms that contribute to cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL112955-04
Application #
8849304
Study Section
Special Emphasis Panel (ZHL1-CSR-X (F1))
Program Officer
Stoney, Catherine
Project Start
2012-05-01
Project End
2017-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
4
Fiscal Year
2015
Total Cost
$164,363
Indirect Cost
$12,175
Name
University of California San Francisco
Department
Psychiatry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Dalgaard, Vita Ligaya; Aschbacher, Kirstin; Andersen, Johan Hviid et al. (2017) Return to work after work-related stress: a randomized controlled trial of a work-focused cognitive behavioral intervention. Scand J Work Environ Health 43:436-446
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