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Is plasminogen activator inhibitor‐1 a physiological bottleneck bridging major depressive disorder and cardiovascular disease?

Savoy, C. ; Van Lieshout, R. J. ; Steiner, M.

Acta Physiologica, April 2017, Vol.219(4), pp.715-727 [Peer Reviewed Journal]

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  • Title:
    Is plasminogen activator inhibitor‐1 a physiological bottleneck bridging major depressive disorder and cardiovascular disease?
  • Author: Savoy, C. ; Van Lieshout, R. J. ; Steiner, M.
  • Description: Major depressive disorder () is estimated to affect one in twenty people worldwide. is highly comorbid with cardiovascular disease (), itself one of the single largest causes of mortality worldwide. A number of pathological changes observed in are believed to contribute to the development of cardiovascular disease, although no single mechanism has been identified. There are also no biological markers capable of predicting the future risk of developing heart disease in depressed individuals. Plasminogen activator inhibitor‐1 (‐1) is a prothrombotic plasma protein secreted by endothelial tissue and has long been implicated in . An expanding body of literature has recently implicated it in the pathogenesis of major depressive disorder as well. In this study, we review candidate pathways implicating in and consider how ‐1 might act as a mediator by which induces development: chiefly through sleep disruption, adiposity, brain‐derived neurotrophic factor () metabolism, systemic inflammation and hypothalamic–pituitary–adrenal ()‐axis dysregulation. As both and are more prevalent in women than in men, and incidence of either condition is dramatically increased during reproductive milestones, we also explore hormonal and sex‐specific associations between ,‐1 and . Of special interest is the role ‐1 plays in perinatal depression and in cardiovascular complications of pregnancy. Finally, we propose a theoretical model whereby ‐1 might serve as a useful biomarker for risk in those with depression, and as a potential target for future treatments.
  • Is Part Of: Acta Physiologica, April 2017, Vol.219(4), pp.715-727
  • Identifier: ISSN: 1748-1708 ; E-ISSN: 1748-1716 ; DOI: 10.1111/apha.12726
  • Subjects: Cardiovascular Disease ; Major Depressive Disorder ; Pregnancy ; Thrombosis ; Women'S Health

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