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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.

SUBMITTER: Aschbacher K

PROVIDER: S-EPMC4808379 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo.

Aschbacher Kirstin K Derakhshandeh Ronak R Flores Abdiel J AJ Narayan Shilpa S Mendes Wendy Berry WB Springer Matthew L ML

Psychoneuroendocrinology 20160223

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 Ame ...[more]

PMID: 26925833

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Project description:BACKGROUND:Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in the term placenta in an ex vivo human placental perfusion model. The placentas used in the experiments were donated from families participating in the Maternal Stress and Placental Function project with a known maternal stress background. METHOD:Cortisol, cortisone, tryptophan and serotonin were added simultaneously to the maternal side in the 6 hour ex vivo term human recirculating placental perfusion model, in four experimental set-ups: without inhibitors, with carbenoxolone -that inhibits cortisol metabolism into cortisone, with fluoxetine that inhibits the serotonin transporter, and with PCPA that inhibits metabolism of tryptophan into serotonin. The concentration of cortisol and cortisone, and tryptophan and serotonin were quantified using UPLC and HPLC-MS respectively. RESULTS:Cortisol was rapidly metabolized into cortisone in the placenta, to a somewhat lesser degree when adding the inhibitor carbenoxolone, resulting in higher fetal exposure to cortisol. Serotonin was also rapidly metabolized in the placenta. When adding fluoxetine a peak of fetal serotonin levels was seen in the first hour of the perfusion. No effect was seen of the maternal stress levels on placental transport kinetics in this study. CONCLUSION:Inhibiting the metabolism of cortisol in the placenta increased fetal exposure to cortisol as expected. Unexpectedly we saw an increased fetal exposure to serotonin when inhibiting the serotonin transporter, which may be related to the increased serotonin concentration on the maternal side of the placenta. No effect on placental kinetics were evident on maternal stress levels during the pregnancy as the majority of participating mothers had normal stress levels.

Project description:BackgroundPsychological stress is a crucial parameter in defining the symptoms of burning mouth syndrome (BMS). We hypothesized that the level of psychological stress in patients with BMS would correlate with severity of clinical symptoms, cortisol levels, and cortisol/ adrenocorticotropic hormone (ACTH) ratio. We aimed to comprehensively investigate the influence of clinical and hematologic parameters on the hypothalamic-pituitary-adrenal axis, particularly concerning the presence or absence of self-perceived psychological stress in patients with BMS. In addition, we aimed to identify parameters predicting psychological stress in these patients.MethodsOne hundred and forty-one patients with BMS (117 women, 82.98%; 56.21 ± 13.92 years) were divided into psychological stress (n = 68; 55 females, 56.39 ± 12.89 years) and non-psychological stress groups (n = 73; 62 females, 56.03 ± 14.90 years), and inter- and intra-group statistical analyses were conducted. Significant predictors of psychological stress in patients with BMS were investigated through multiple logistic regression analysis.ResultsThe prevalence of xerostomia was significantly higher (67.6% vs. 34.2%, p < 0.001), while unstimulated salivary flow rate was lower (0.66 ± 0.59 vs. 0.91 ± 0.53 mL/min, p < 0.01) in the psychological stress group than in the non-psychological stress group. SCL-90R subscale values for somatization, hostility, anxiety, and depression, as well as cortisol and ACTH levels and the cortisol/ACTH ratio, were also higher in the psychological stress group (all p < 0.05). Above-mean values for cortisol (AUC = 0.980, 95%CI: 0.959-1.000) and cortisol/ACTH (AUC = 0.779; 95%CI, 0.701-0.856) were excellent predictors of psychological stress, with cortisol (r = 0.831, p < 0.01) and cortisol/ACTH (r = 0.482, p < 0.01) demonstrating substantial correlations. Above-average values for cortisol (OR = 446.73) and cortisol/ACTH (OR = 6.159) significantly increased incidence of psychological stress in patients with BMS (all p < 0.001).ConclusionsAmong patients with BMS, xerostomia, decreased salivary flow rate, increased cortisol levels, and cortisol/ACTH ratio were associated with psychological stress, highlighting the psycho-neuro-endocrinological features of this condition. Cortisol and cortisol/ACTH ratio were strong predictors of psychological stress in patients with BMS.

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Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo.

Publications

Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo.

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