Glyceryl trinitrate inhibits hypoxia-induced release of soluble fms-like tyrosine kinase-1 and endoglin from placental tissues

Ivraym B Barsoum, Stephen J Renaud, Charles H Graham
American Journal of Pathology 2011, 178 (6): 2888-96
Preeclampsia is associated with increased circulating levels of proinflammatory molecules, such as soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng). On release by an inadequately perfused placenta into the maternal circulation, these molecules cause systemic endothelial dysfunction and the associated hypertension and proteinuria that characterize preeclampsia. We previously showed that glyceryl trinitrate (GTN) inhibits hypoxia/reoxygenation-induced apoptosis in the syncytiotrophoblast of term chorionic villi explants. Herein, we demonstrate that GTN inhibits the release of sFlt-1 and sEng from term chorionic villi explants exposed to hypoxia. Although transcript levels and secretion of sFlt-1 and sEng increased in explants exposed to hypoxia, low concentrations of GTN significantly inhibited the hypoxia-induced expression of these molecules at the mRNA and protein levels. Treatment of explants with GTN also prevented the hypoxia-induced accumulation of hypoxia-inducible factor-1α, a key mediator of cellular adaptations to hypoxia. Furthermore, knockdown of hypoxia-inducible factor-1α inhibited the hypoxia-induced secretion of sFlt-1 and sEng. This study provides evidence that hypoxia induces the release of sFlt-1 and sEng in the placenta via a mechanism that is inhibited by low concentrations of GTN. Our findings indicate that GTN may have potential applications in the treatment and/or prevention of preeclampsia.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"