OBJECTIVE: An increasing number of studies have examined the role of emotional stress and coronary heart disease; the underlying pathophysiology is still poorly understood. The present study was designed to evaluate the relationship between acute (epi- and norepinephrine) and chronic stress hormones (dexamethasone, beta-endorphin, corticotropin releasing hormone) and endothelial dysfunction. METHODS: Human microvascular endothelial cells were incubated with stress hormones for 6 and 24 h. ET-1 release and ADMA were quantified via ELISA, NO release by using cell permeable 4.5-diaminofluorescein diacetate (DAF2-DA), oxidative stress fluometrically by the ROS-sensitive carboxy-H2-DCFDA method, mitochondrial metabolic activity by using the colorimetric assay WST-1, ET-1 receptor type A (ET(A)R) protein expression by Western blot, and cell proliferation activity was assessed by the colorimetric assay BrdU. RESULTS: With respect to analysed acute and chronic stress hormones, ET-1 release was significantly increased. Likewise, protein expression was enhanced after long term incubation (24 h) with norepinephrine and dexamethasone. In contrast, endothelial NO-levels were only influenced by short term stimulation of dexamethasone (upregulation of NO release) and norepinephrine (downregulation of NO release), whereas modified NO concentration mimics altered mitochondrial metabolic activity. Unexpectedly, both oxidative stress and cell proliferation were not modified by stress hormones. CONCLUSION: Results suggest that acute and chronic stress hormones induce a significant ET-1 release whereas NO release remained mainly unchanged. The imbalance of pro- and antiatherosclerotic factors may play a pivotal role in the initiation of stress-related endothelial dysfunction up to myocardial infarction.
OBJECTIVE: An increasing number of studies have examined the role of emotional stress and coronary heart disease; the underlying pathophysiology is still poorly understood. The present study was designed to evaluate the relationship between acute (epi- and norepinephrine) and chronic stress hormones (dexamethasone, beta-endorphin, corticotropin releasing hormone) and endothelial dysfunction. METHODS:Human microvascular endothelial cells were incubated with stress hormones for 6 and 24 h. ET-1 release and ADMA were quantified via ELISA, NO release by using cell permeable 4.5-diaminofluorescein diacetate (DAF2-DA), oxidative stress fluometrically by the ROS-sensitive carboxy-H2-DCFDA method, mitochondrial metabolic activity by using the colorimetric assay WST-1, ET-1 receptor type A (ET(A)R) protein expression by Western blot, and cell proliferation activity was assessed by the colorimetric assay BrdU. RESULTS: With respect to analysed acute and chronic stress hormones, ET-1 release was significantly increased. Likewise, protein expression was enhanced after long term incubation (24 h) with norepinephrine and dexamethasone. In contrast, endothelial NO-levels were only influenced by short term stimulation of dexamethasone (upregulation of NO release) and norepinephrine (downregulation of NO release), whereas modified NO concentration mimics altered mitochondrial metabolic activity. Unexpectedly, both oxidative stress and cell proliferation were not modified by stress hormones. CONCLUSION: Results suggest that acute and chronic stress hormones induce a significant ET-1 release whereas NO release remained mainly unchanged. The imbalance of pro- and antiatherosclerotic factors may play a pivotal role in the initiation of stress-related endothelial dysfunction up to myocardial infarction.
Authors: Brandon M Fox; Bryan K Becker; Analia S Loria; Kelly A Hyndman; Chunhua Jin; Hannah Clark; Robin Johns; Masashi Yanagisawa; David M Pollock; Jennifer S Pollock Journal: J Am Heart Assoc Date: 2018-02-16 Impact factor: 5.501