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OxLDL sensitizes pl...
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Maaninka, KatariinaUniv Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Grp, Helsinki, Finland.;Univ Helsinki, Fac Pharm, Drug Res Program, Div Pharmaceut Biosci,CURED, Helsinki, Finland.;Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Core, Helsinki, Finland.
(författare)
OxLDL sensitizes platelets for increased formation of extracellular vesicles capable of finetuning macrophage gene expression
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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Elsevier,2023
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-500655
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-500655URI
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https://doi.org/10.1016/j.ejcb.2023.151311DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Platelet extracellular vesicles (PEVs) generated upon platelet activation may play a role in inflammatory pathologies such as atherosclerosis. Oxidized low-density lipoprotein (oxLDL), a well-known contributor to atherogenesis, activates platelets and presensitizes them for activation by other agonists. We studied the effect of oxLDL on the secretion, composition, and inflammatory functions of PEVs using contemporary EV analytics. Platelets were activated by co-stimulation with thrombin (T) and collagen (C) ± oxLDL and characterized by high-resolution flow cytometry, nanoparticle tracking analysis, proximity extension assay, western blot, and electron microscopy. The effect of PEVs on macrophage differentiation and functionality was examined by analyzing macrophage surface markers, cytokine secretion, and transcriptome. OxLDL upregulated TC-induced formation of CD61+, P-selectin+ and phosphatidylserine+ PEVs. Blocking the scavenger receptor CD36 significantly suppressed the oxLDL+TC-induced PEV formation, and HDL caused a slight but detectable suppression. The inflammatory protein cargo differed between the PEVs from stimulated and unstimulated platelets. Both oxLDL+TC- and TC-induced PEVs enhanced macrophage HLA-DR and CD86 expression and decreased CD11c expression as well as secretion of several cytokines. Pathways related to cell cycle and regulation of gene expression, and immune system signaling were overrepresented in the differentially expressed genes between TC PEV -treated vs. control macrophages and oxLDL+TC PEV -treated vs. control macrophages, respectively. In conclusion, we speculate that oxLDL and activated platelets contribute to proatherogenic processes by increasing the number of PEVs that provide an adhesive and procoagulant surface, contain inflammatory mediators, and subtly finetune the macrophage gene expression.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Neuvonen, MaaritUniv Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Grp, Helsinki, Finland.;Univ Helsinki, Fac Pharm, Drug Res Program, Div Pharmaceut Biosci,CURED, Helsinki, Finland.
(författare)
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Kerkelä, ErjaFinnish Red Cross Blood Serv FRCBS, Helsinki, Finland.
(författare)
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Hyvärinen, KatiFinnish Red Cross Blood Serv FRCBS, Helsinki, Finland.
(författare)
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Palviainen, MariUniv Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Grp, Helsinki, Finland.;Univ Helsinki, Fac Pharm, Drug Res Program, Div Pharmaceut Biosci,CURED, Helsinki, Finland.;Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Core, Helsinki, Finland.
(författare)
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Kamali-Moghaddam, MasoodUppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylära verktyg och funktionsgenomik(Swepub:uu)masookam
(författare)
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Federico, AntonioTampere Univ, Fac Med & Hlth Technol, Finnish Hub Dev & Validat Integrated Approaches F, Tampere, Finland.
(författare)
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Greco, DarioTampere Univ, Fac Med & Hlth Technol, Finnish Hub Dev & Validat Integrated Approaches F, Tampere, Finland.;Univ Helsinki, Fac Pharm, Div Pharmaceut Biosci, Helsinki, Finland.
(författare)
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Laitinen, SaaraFinnish Red Cross Blood Serv FRCBS, Helsinki, Finland.
(författare)
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Öörni, KatariinaWihuri Res Inst, Atherosclerosis Res Lab, Helsinki, Finland.
(författare)
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Siljander, Pia R. M.Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Grp, Helsinki, Finland.;Univ Helsinki, Fac Pharm, Drug Res Program, Div Pharmaceut Biosci,CURED, Helsinki, Finland.;Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Core, Helsinki, Finland.
(författare)
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Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Grp, Helsinki, Finland.;Univ Helsinki, Fac Pharm, Drug Res Program, Div Pharmaceut Biosci,CURED, Helsinki, Finland.;Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Core, Helsinki, Finland.Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Grp, Helsinki, Finland.;Univ Helsinki, Fac Pharm, Drug Res Program, Div Pharmaceut Biosci,CURED, Helsinki, Finland.
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:European Journal of Cell Biology: Elsevier102:20171-93351618-1298
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Maaninka, Katari ...
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Neuvonen, Maarit
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Kerkelä, Erja
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Hyvärinen, Kati
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Palviainen, Mari
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Kamali-Moghaddam ...
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Federico, Antoni ...
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Greco, Dario
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Laitinen, Saara
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Öörni, Katariina
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Siljander, Pia R ...
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