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dc.contributor.authorOkamoto, Yoshihisa
dc.contributor.authorIshii, So
dc.contributor.authorCroce, Kevin James
dc.contributor.authorKatsumata, Harumi
dc.contributor.authorFukushima, Makoto
dc.contributor.authorKihara, Shinji
dc.contributor.authorLibby, Peter
dc.contributor.authorMinami, Shiro
dc.date.accessioned2017-04-27T19:45:17Z
dc.date.issued2013
dc.identifier.citationOkamoto, Yoshihisa, So Ishii, Kevin Croce, Harumi Katsumata, Makoto Fukushima, Shinji Kihara, Peter Libby, and Shiro Minami. 2013. “Adiponectin Inhibits Macrophage Tissue Factor, a Key Trigger of Thrombosis in Disrupted Atherosclerotic Plaques.” Atherosclerosis 226 (2) (February): 373–377. doi:10.1016/j.atherosclerosis.2012.12.012.en_US
dc.identifier.issn0021-9150en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32605321
dc.description.abstractObjective Adiponectin (APN) is an adipocytokine with anti-atherogenic and anti-inflammatory properties. Hypoadiponectinemia may associate with increased risk for coronary artery disease (CAD) and acute coronary syndrome (ACS). Tissue factor (TF) initiates thrombus formation and facilitates luminal occlusion after plaque rupture, a common cause of fatal ACS. This study tested the hypothesis that APN influences TF expression by macrophages (MΦ), inflammatory cells found in atheromatous plaques. Methods Human monocyte-derived MΦ or RAW 264.7 cells transfected with TF promoter construct, pretreated with a physiological range of recombinant APN (1–10 μg/ml), received LPS stimulation. TF mRNA and protein levels were quantified by real-time RT-PCR and ELISA. TF pro-coagulant activity was evaluated by one-step clotting assay. TF promoter activity was determined by a dual-luciferase reporter assay. Immunoblot analyses assessed intracellular signaling pathways. Results APN treatment suppressed TF mRNA expression and protein production in LPS-stimulated human MΦ, compared to vehicle controls. APN treatment also significantly reduced TF pro-coagulant activity in lysates of LPS-stimulated human MΦ, compared to vehicle controls. Moreover, APN suppressed TF promoter activity in LPS-stimulated MΦ compared to controls. APN suppressed phosphorylation and degradation of IκB-α in LPS-stimulated MΦ. Conclusions APN reduces thrombogenic potential of MΦ by inhibiting TF expression and activity. These observations provide a potential mechanistic link between low APN levels and the thrombotic complications of atherosclerosis.en_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.relation.isversionofdoi:10.1016/j.atherosclerosis.2012.12.012en_US
dc.relation.hasversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580852/en_US
dash.licenseLAA
dc.subjectAdiponectinen_US
dc.subjectTissue factoren_US
dc.subjectMacrophageen_US
dc.subjectAtherothrombosisen_US
dc.titleAdiponectin inhibits macrophage tissue factor, a key trigger of thrombosis in disrupted atherosclerotic plaquesen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalAtherosclerosisen_US
dash.depositing.authorLibby, Peter
dc.date.available2017-04-27T19:45:17Z
dc.identifier.doi10.1016/j.atherosclerosis.2012.12.012*
dash.contributor.affiliatedCroce, Kevin
dash.contributor.affiliatedLibby, Peter
dc.identifier.orcid0000-0002-1502-502X


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