Disturbed Redox Homeostasis in Oxidative Distress
A Molecular Link From Chronic Psychosocial Work Stress to Coronary Heart Disease?
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Epidemiology generates interest by providing plausible associations, and biochemistry and molecular biology attempt to pin down cause– effect relationships in concrete molecular terms. In this Viewpoint, we posit that coronary heart disease (CHD) and its relationship to work stress may qualify as prime example of an entity that profits from recent advances in these 2 areas of research. Relationships to hydrogen peroxide (H2O2) and ion channels provide clues for elucidating molecular pathophysiology related to psychosocial stress.
The cardiovascular system is a target of psychosocial stress. The pathophysiological chain of events linking chronic psychosocial stress with cardiovascular disease (CVD) includes dysregulation in the hypothalamic–pituitary–adrenal axis and in the autonomic nervous system. Among the physiological changes are increased heart rate, increased blood pressure, energy mobilization, decreased insulin sensitivity, and endothelial dysfunction.1 These processes may ultimately result in manifest CVD. In terms of population health, the largest part of the burden of CVD is attributed to CHD. Epidemiological associations of chronic psychosocial stress at work, a core social stressor in modern life, with CHD have been repeatedly confirmed (see below). For instance, in a recent multicohort study of 90 164 individuals, the simultaneous exposure to 2 major forms of chronic psychosocial stress at work, job strain and effort–reward imbalance, revealed a 1.4-fold increase in risk for incident CHD.2 Much needs to be learned on the molecular signals involved.
Role of Oxidative Distress in CHD Development
There is evidence linking psychosocial stress to mononuclear cell activation via nuclear factor κB.3 Fine tuning of major molecular redox switches, such as nuclear factor κB and nuclear factor E2–related factor 2/Kelch-like ECH-associated protein 1, is a central focus in current …