Synthesis of sFlt-1 by platelet-monocyte aggregates contributes to the pathogenesis of preeclampsia

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• 作者：Heather D. Major ; MD^a ; Robert A. Campbell ; PhD^b ; Robert M. Silver ; MD^a ; D. Ware Branch ; MD^a ; Andrew S. Weyrich ; PhD^b ; ^{andy.weyrich@u2m2.utah.edu" class="auth_mail}
• 关键词：platelet-monocyte aggregates ; preeclampsia ; sFlt-1
• 刊名：American Journal of Obstetrics and Gynecology
• 出版年：June 2014
• 年：2014
• 卷：210
• 期：6
• 页码：547.e1-547.e7
• 全文大小：706 K

文摘

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-魏B–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.