title: Endothelial microparticles reduce ICAM-1 expression in a microRNA-222-dependent mechanism.
abstract: Endothelial microparticles (EMP) are released from activated or apoptotic endothelial cells (ECs) and can be taken up by adjacent ECs, but their effect on vascular inflammation after engulfment is largely unknown. We sought to determine the role of EMP in EC inflammation. In vitro, EMP treatment significantly reduced tumour necrosis factor-α-induced endothelial intercellular adhesion molecule (ICAM)-1 expression on mRNA and protein level, whereas there was no effect on vascular cell adhesion molecule-1 expression. Reduced ICAM-1 expression after EMP treatment resulted in diminished monocyte adhesion in vitro. In vivo, systemic treatment of ApoE-/- mice with EMP significantly reduced murine endothelial ICAM-1 expression. To explore the underlying mechanisms, Taqman microRNA array was performed and microRNA (miR)-222 was identified as the strongest regulated miR between EMP and ECs. Following experiments demonstrated that miR-222 was transported into recipient ECs by EMP and functionally regulated expression of its target protein ICAM-1 in vitro and in vivo. After simulating diabetic conditions, EMP derived from glucose-treated ECs contained significantly lower amounts of miR-222 and showed reduced anti-inflammatory capacity in vitro and in vivo. Finally, circulating miR-222 level was diminished in patients with coronary artery disease (CAD) compared to patients without CAD. EMPs promote anti-inflammatory effects in vitro and in vivo by reducing endothelial ICAM-1 expression via the transfer of functional miR-222 into recipient cells. In pathological hyperglycaemic conditions, EMP-mediated miR-222-dependent anti-inflammatory effects are reduced.
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Jansen
authors.affiliation: Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Baumann
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Przybilla
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Schmitz
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Flender
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Paul
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Adil
authors.initials: A
authors.lastname: Alhusseiny
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Nikos
authors.initials: N
authors.lastname: Werner
mesh_terms: D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D005947:Glucose; D018799:Intercellular Adhesion Molecule-1; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; C525710:MIR222, human; C546123:MIRN222 microRNA, mouse
keywords: ICAM-1; endothelial microparticles; inflammation; microRNA-222