Show simple item record

AuthorSafiedeen, Zainab
AuthorRodríguez-Gómez, Isabel
AuthorVergori, Luisa
AuthorSoleti, Raffaella
AuthorVaithilingam, Dayannath
AuthorDouma, Imene
AuthorAgouni, Abdelali
AuthorLeiber, Denis
AuthorDubois, Séverine
AuthorSimard, Gilles
AuthorZibara, Kazem
AuthorAndriantsitohaina, Ramaroson
AuthorMartínez, M. Carmen
Available date2017-04-16T08:05:24Z
Publication Date2017-01-01
Publication NameAntioxidants & Redox Signalingen_US
Identifierhttp://dx.doi.org/10.1089/ars.2016.6771
Citation"Temporal Cross Talk Between Endoplasmic Reticulum and Mitochondria Regulates Oxidative Stress and Mediates Microparticle-Induced Endothelial Dysfunction" Safiedeen Zainab, Rodríguez-Gómez Isabel, Vergori Luisa, Soleti Raffaella, Vaithilingam Dayannath, Douma Imene, Agouni Abdelali, Leiber Denis, Dubois Séverine, Simard Gilles, Zibara Kazem, Andriantsitohaina Ramaroson, and Martínez M. Carmen. Antioxidants & Redox Signaling. January 2017, 26(1): 15-27
ISSN1523-0864
URIhttp://hdl.handle.net/10576/5462
AbstractAims: Circulating microparticles (MPs) from metabolic syndrome patients and those generated from apoptotic T-cells induce endothelial dysfunction; however, the molecular and cellular mechanism(s) underlying in the effects of MPs remain to be elucidated. Results: Here, we show that both types of MPs increased expression of endoplasmic reticulum (ER) stress markers XBP-1, p-eIF2alpha and CHOP and nuclear translocation of ATF6 on human aortic endothelial cells. MPs decreased in vitro nitric oxide release by human aortic endothelial cells, whereas in vivo MP injection into mice impaired the endothelium-dependent relaxation induced by acetylcholine. These effects were prevented when ER stress was inhibited suggesting that ER stress is implicated in the endothelial effects induced by MPs. MPs affected mitochondrial function and evoked sequential increase of cytosolic and mitochondrial reactive oxygen species (ROS). Pharmacological inhibition of ER stress and silencing of neutral sphingomyelinase with siRNA abrogated all MP-mediated effects. Neutralization of Fas-Ligand carried by MPs abolished effects induced by both MP types, whereas neutralization of low density lipoprotein-receptor on endothelial cells prevented T-lymphocyte MP-mediated effects. Innovation and Conclusion: Collectively, endothelial dysfunction triggered by MPs involves temporal cross-talk between ER and mitochondria with respect to spatial regulation of ROS via the neutral sphingomyelinase and interaction of MPs with Fas and/or low density lipoprotein-receptor. These results provide a novel molecular insight into the manner MPs mediate vascular dysfunction and allow identification of potential therapeutic targets to treat vascular complications associated with metabolic syndrome.
SponsorInstitut National de la Santé et de la Recherche Médicale, Université dʼAngers and Centre Hospitalo-Universitaire dʼAngers.
Languageen
PublisherMary Ann Liebert, Inc.
SubjectER stress
SubjectMicroparticles
SubjectEndothelial dysfunction
TitleTemporal cross talk between endoplasmic reticulum and mitochondria regulates oxidative stress and mediates microparticle-induced endothelial dysfunction
TypeArticle
Pagination15-27
Issue Number1
Volume Number26
ESSN1557-7716


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record