Detrimental arterial inflammatory effect of microparticles circulating in preeclamptic women: ex vivo evaluation in human arteries

Julie Boisramé-Helms (1) , Ferhat Meziani (1, 2) , Nicolas Sananès , Thomas Boisramé , Bruno Langer (3) , Francis Schneider (4) , Thierry Ragot (5) , Ramaroson Andriantsitohaina (6) , Angela Tesse (7)

1 Service de Réanimation Médicale [Strasbourg]
2 FMTS - Fédération de Médecine Translationnelle de Strasbourg
3 Service de gynécologie–obstétrique
4 Hôpital de Hautepierre [Strasbourg]
5 UMR 8203 - Vectorologie et thérapeutiques anti-cancéreuses [Villejuif]
6 SOPAM - Stress Oxydant et Pathologies Métaboliques
7 ITX - ITX - unité de recherche de l'institut du thorax

Elevated plasmatic levels of lympho-monocyte and platelet microparticles (MPs) have been reported in preeclampsia. Previous studies suggest that MPs could participate in preeclampsia vascular impairment. In this study, we investigated the ex vivo vascular effects of MPs from preeclamptic women on arteries from normotensive pregnant women. Omental arteries were collected from normal pregnant women undergoing cesarean section and incubated during 24 h with MPs from normal pregnant or preeclamptic women. Vascular contraction to serotonin and phenylephrine was studied on a wire myograph with or without pharmacological selective inhibitors of inducible nitric oxide synthase (iNOS) and/or cyclo-oxygenase-2 (COX-2). Expression of iNOS, COX-2, and NF-κB and production of superoxide anion and 8-isoprostane were also assessed by immunohistological or biochemical staining and/or Western blot or ELISA assay, respectively. Microparticles from preeclamptic women, but not those from normal pregnant women, induced hyporeactivity to vasocontracturant agonists in omental arteries. Selective inhibitor of iNOS partially restored this arterial contraction, suggesting that nitric oxide (NO) is involved in vascular contractility alteration. Conversely, COX-2 induced 8-isoprostane release, a vasoconstricting metabolite modulating the agonist-induced contraction. COX-2 selective inhibitor almost abolished the arterial contraction in the same vessels. Interestingly, the association of iNOS and COX-2 selective inhibitors restored the contraction to control levels. Moreover, iNOS, COX-2, and NF-κB expressions are upregulated and superoxide anion levels increased in vessels incubated with MPs from preeclamptic women. In conclusion, circulating MPs from preeclamptic women induce vascular inflammation and enhance oxidative stress. These results suggest a possible role of MPs during preeclampsia-induced arterial dysfunction.

Mots clés: Female; Signal Transduction; Pregnancy; Young Adult; Cell-Derived Microparticles; Nitric Oxide; Cyclooxygenase 2; Nitric Oxide Synthase Type II; Dose-Response Relationship; Drug; NF-kappa B; Hypertension; Inflammation Mediators; Arteries; Vasoconstriction; Vasoconstrictor Agents; Pre-Eclampsia; Cyclooxygenase 2 Inhibitors; Omentum; preeclampsia; Tissue Culture Techniques; vascular inflammation; humans; adult; Oxidative stress; hypertension; nitric oxide; preeclampsia; pregnancy; vascular inflammation

Domaines: Sciences du Vivant [q-bio]

Julie Boisramé-Helms, Ferhat Meziani, Nicolas Sananès, Thomas Boisramé, Bruno Langer, et al.. Detrimental arterial inflammatory effect of microparticles circulating in preeclamptic women: ex vivo evaluation in human arteries. Fundamental & Clinical Pharmacology, 2015, Equipe 2, 29 (5), pp.450--461. ⟨10.1111/fcp.12136⟩. ⟨hal-01830586⟩