Interaction Between Platelets and Cytokines - A Possible Role in the Pathogenesis of Preeclampsia

Author(s): Jacob Bar , Avi Ben-Haroush , Judith Lahav , Mark Sullivan .

Journal Name: Vascular Disease Prevention

Volume 1 , Issue 2 , 2004

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Abstract:

Preeclampsia has recently been suggested to be a two-stage disorder of an alteration in placental perfusion (stage 1) leading to a maternal syndrome (stage 2). However, the mechanism linking the two remains unclear. There is now cumulative evidence that platelets may be involved. Platelets are known to be activated in early normal pregnancy, and their increased activation and consumption is probably controlled by yet unknown buffering factors that maintain hemostasis and prevent further platelet activation. Further platelet activation that is affected by cytokines, especially TNF- α and by IL-1β, by currently unknown mechanisms, occurs weeks to months before the clinical appearance of preeclampsia. We found that maternal platelet function undergoes marked changes during normal pregnancy toward refractoriness to activation by IL-1β and TNF-α. In preeclampsia, this refractoriness is lost or diminished due to an intrinsic change in platelet response and, at least in the case of IL-1β, reverts toward the non-pregnant state. Failure to control the stimulatory platelet changes of pregnancy leads to platelet adhesion, aggregation, and release of thromboxane A2, which in turn, generate vasoconstriction, further aggregation, and progressive damage to endothelial cells. CD40 ligand (a transmembrane protein structurally related to TNF-α) is shed from activated platelets to directly initiate inflammation of the vessel wall. On the basis of these findings, we propose that the complex interaction between activated platelets and impaired cytokine production at the feto-maternal interface, triggered by immunological or inflammatory factors in the early stages of pregnancy, contributes to the evolution of preeclampsia.

Keywords: preeclampsia, maternal syndrome, platelet activation, vasoconstriction

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Article Details

VOLUME: 1
ISSUE: 2
Year: 2004
Page: [101 - 107]
Pages: 7
DOI: 10.2174/1567270010401020101
Price: $58

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