Hydroxychloroquine reverses the prothrombotic state in a mouse model of antiphospholipid syndrome: Role of reduced inflammation and endothelial dysfunction

Abstract : Antiphospholipid antibodies (aPL) promote endothelial dysfunction, inflammation and pro-coagulant state. We investigated the effect of hydroxychloroquine (HCQ) on prothrombotic state and endothelial function in mice and in human aortic endothelial cells (HAEC). Human aPL were injected to C57BL/6 mice treated or not with HCQ. Vascular endothelial function and eNOS were assessed in isolated mesenteric arteries. Thrombosis was assessed both in vitro by measuring thrombin generation time (TGT) and tissue factor (TF) expression and in vivo by the measurement of the time to occlusion in carotid and the total thrombosis area in mesenteric arteries. TGT, TF, and VCAM1 expression were evaluated in HAEC. aPL increased VCAM-1 expression and reduced endothelium dependent relaxation to acetylcho-line. In parallel, aPL shortened the time to occlusion and extended thrombus area in mice. This was associated with an overexpression of TF and an increased TGT in mice and in HAEC. HCQ reduced clot formation as well as TGT, and improved endothelial-dependent relaxations. Finally, HCQ increased the p-eNOS/eNOS ratio. This study provides new evidence that HCQ improves procoagulant status and vascular function in APS by modulating eNOS, leading to an improvement in the production of NO.
Complete list of metadatas

Cited literature [38 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02296602
Contributor : Ebba Brakenhielm <>
Submitted on : Wednesday, September 25, 2019 - 12:32:08 PM
Last modification on : Friday, September 27, 2019 - 1:22:01 AM

File

Miranda Hydroxychloroquine.pdf
Publisher files allowed on an open archive

Identifiers

Citation

Sébastien Miranda, Paul Billoir, Louise Damian, Pierre Alain Thiebaut, Damien Schapman, et al.. Hydroxychloroquine reverses the prothrombotic state in a mouse model of antiphospholipid syndrome: Role of reduced inflammation and endothelial dysfunction. PLoS ONE, Public Library of Science, 2019, 14 (3), pp.e0212614. ⟨10.1371/journal.pone.0212614⟩. ⟨inserm-02296602⟩

Share

Metrics

Record views

18

Files downloads

49