Abstract
Objective Soluble fms-like tyrosine kinase (sFlt-1) is an important mediator in the pathogenesis of preeclampsia. We sought to determine whether platelet-monocyte aggregates (PMAs) produced sFlt-1 and whether PMAs contributed to sFlt-1 production in preeclampsia. Study Design This was a case-control study of sFlt-1 release from PMAs using blood samples from women with preeclampsia matched by gestational age to pregnant controls. A third group of nonpregnant, reproductive-age women comprised an additional control group. Experiments were also performed using blood from nonpregnant women to elucidate whether inducing PMAs could stimulate sFlt-1 production and, if so, to determine the necessary receptors and pathways. Results Women with preeclampsia had increased total Flt-1 concentrations in platelets and monocytes at baseline compared with pregnant controls (25 vs 10 pg/mL, P =.0003). sFlt-1 production was elicited from monocytes incubated with thrombin-activated platelets from nonpregnant women. sFlt-1 production was regulated at the transcriptional level by p38 and nuclear factor-κB-dependent pathways. Conclusion Activated platelets in preeclampsia bind monocytes to generate sFlt-1. PMAs are a previously unrecognized source of sFlt-1 that may contribute to endothelial dysfunction and systemic inflammation commonly observed in preeclampsia.
Original language | English |
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Pages (from-to) | 547.e1-547.e7 |
Journal | American journal of obstetrics and gynecology |
Volume | 210 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2014 |
Keywords
- platelet-monocyte aggregates
- preeclampsia
- sFlt-1