dc.contributor.author | Colas, RA | en_US |
dc.contributor.author | Souza, PR | en_US |
dc.contributor.author | Walker, ME | en_US |
dc.contributor.author | Burton, M | en_US |
dc.contributor.author | Zasłona, Z | en_US |
dc.contributor.author | Curtis, AM | en_US |
dc.contributor.author | Marques, RM | en_US |
dc.contributor.author | Dalli, J | en_US |
dc.date.accessioned | 2019-02-05T09:57:27Z | |
dc.date.available | 2018-02-02 | en_US |
dc.date.issued | 2018-03-16 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/55164 | |
dc.description.abstract | RATIONALE: Diurnal mechanisms are central to regulating host responses. Recent studies uncovered a novel family of mediators termed as specialized proresolving mediators that terminate inflammation without interfering with the immune response. OBJECTIVE: Herein, we investigated the diurnal regulation of specialized proresolving mediators in humans and their role in controlling peripheral blood leukocyte and platelet activation. METHODS AND RESULTS: Using lipid mediator profiling and healthy volunteers, we found that plasma concentrations of n-3 docosapentaenoic acid-derived D-series resolvins (RvDn-3 DPA) were regulated in a diurnal manner. The production and regulation of these mediators was markedly altered in patients at risk of myocardial infarct. These changes were associated with decreased 5-lipoxygenase expression and activity, as well as increased systemic adenosine concentrations. We also found a significant negative correlation between plasma RvDn-3 DPA and markers of platelet, monocyte, and neutrophil activation, including CD63 and CD11b. Incubation of RvDn-3 DPA with peripheral blood from healthy volunteers and patients with cardiovascular disease significantly and dose-dependently decreased platelet and leukocyte activation. Furthermore, administration of RvD5n-3 DPA to ApoE-/- (apolipoprotein E deficient) mice significantly reduced platelet-leukocyte aggregates, vascular thromboxane B2 concentrations, and aortic lesions. CONCLUSIONS: These results demonstrate that peripheral blood RvDn-3 DPA are diurnally regulated in humans, and dysregulation in the production of these mediators may lead to cardiovascular disease. | en_US |
dc.description.sponsorship | Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number: 107613/Z/15/Z), | en_US |
dc.description.sponsorship | European Research Council under the European Union’s Horizon 2020 research and innovation program (grant number: 677542), | en_US |
dc.description.sponsorship | Barts Charity (grant number: MGU0343 | en_US |
dc.description.sponsorship | Medical Research Council Advance Course Masters (grant number: MR/J015741/1) | en_US |
dc.description.sponsorship | Science Foundation Ireland Starting Investigator Research Grant 13/SIRG/2130 | en_US |
dc.description.sponsorship | Wellcome Trust grant 101604/Z/13/Z | en_US |
dc.format.extent | 855 - 863 | en_US |
dc.language | eng | en_US |
dc.language.iso | en_US | en_US |
dc.relation.ispartof | Circ Res | en_US |
dc.rights | Creative Commons Attribution Non-Commercial License | |
dc.subject | adenosine | en_US |
dc.subject | eicosanoids | en_US |
dc.subject | lipoxygenase | en_US |
dc.subject | monocyte | en_US |
dc.subject | neutrophils | en_US |
dc.subject | platelets | en_US |
dc.title | Impaired Production and Diurnal Regulation of Vascular RvDn-3 DPA Increase Systemic Inflammation and Cardiovascular Disease. | en_US |
dc.type | Article | |
dc.rights.holder | © 2018 The Authors. | |
dc.identifier.doi | 10.1161/CIRCRESAHA.117.312472 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29437834 | en_US |
pubs.issue | 6 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 122 | en_US |
dcterms.dateAccepted | 2018-02-02 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |