title: Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo.
abstract: Psychological stress and glucocorticoids are associated with heightened cardiovascular disease risk. We investigated whether stress or cortisol would be associated with reduced circulating angiogenic cell (CAC) function, an index of impaired vascular repair. We hypothesized that minority-race individuals who experience threat in interracial interactions would exhibit reduced CAC function, and that this link might be explained by cortisol. To test this experimentally, we recruited 106 African American participants for a laboratory interracial interaction task, in which they received socially evaluative feedback from Caucasian confederates. On a separate day, a subset of 32 participants (mean age=26years, 47% female) enrolled in a separate biological substudy and provided blood samples for CAC isolation and salivary samples to quantify the morning peak in cortisol (the cortisol awakening response, CAR). CAC function was quantified using cell culture assays of migration to vascular endothelial growth factor (VEGF) and secretion of VEGF into the culture medium. Heightened threat in response to an interracial interaction and trait anxiety in vivo were both associated with poorer CAC migratory function in vitro. Further, threat and poorer sustained attention during the interracial interaction were associated with a higher CAR, which in turn, was related to lower CAC sensitivity to glucocorticoids. In vitro, higher doses of cortisol impaired CAC migratory function and VEGF protein secretion. The glucocorticoid receptor antagonist RU486 reversed this functional impairment. These data identify a novel, neuroendocrine pathway by which psychological stress may reduce CAC function, with potential implications for cardiovascular health.
authors.affiliation: Department of Psychiatry, University of California, 3333 California Street, San Francisco, CA 94143, United States; The Institute for Integrative Health, 1407 Fleet Street, Baltimore, MD 21231, United States. Electronic address: kirstin.aschbacher@ucsf.edu.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Aschbacher
authors.affiliation: Cardiovascular Research Institute, 555 Mission Bay Boulevard South, University of California, San Francisco, CA 94143, United States.
authors.forename: Ronak
authors.initials: R
authors.lastname: Derakhshandeh
authors.affiliation: Department of Psychology, Columbia University, 406 Schermerhorn Hall, 1190 Amsterdam Avenue, New York, NY 10027, United States.
authors.forename: Abdiel J
authors.initials: AJ
authors.lastname: Flores
authors.affiliation: Cardiovascular Research Institute, 555 Mission Bay Boulevard South, University of California, San Francisco, CA 94143, United States.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Narayan
authors.affiliation: Department of Psychiatry, University of California, 3333 California Street, San Francisco, CA 94143, United States.
authors.forename: Wendy Berry
authors.initials: WB
authors.lastname: Mendes
authors.affiliation: Cardiovascular Research Institute, 555 Mission Bay Boulevard South, University of California, San Francisco, CA 94143, United States; Division of Cardiology, University of California, 505 Parnassus Avenue, San Francisco, CA 94143, United States; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, United States.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Springer
mesh_terms: D000328:Adult; D001741:Black or African American / Q000523:psychology; D001007:Anxiety; D001288:Attention; D054443:Cell Migration Assays; D002465:Cell Movement; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D005239:Fear; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007206:Individuality; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D012463:Saliva / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D042461:Vascular Endothelial Growth Factor A; D015735:Mifepristone; D006854:Hydrocortisone
keywords: Angiogenesis; Anxiety; Circulating hematopoietic progenitor cells; Endothelial progenitor cells; Executive function; Sustained attention