TLR accessory molecule RP105 (CD180) is involved in post-interventional vascular remodeling and soluble RP105 modulates neointima formation

Autor: T. Harma C. Brondijk, Erna Peters, J. Wouter Jukema, M.M. Ewing, Hetty C. de Boer, Margreet R. de Vries, Saskia C. A. de Jager, Anton Jan van Zonneveld, Eric G. Huizinga, Johan Kuiper, J.C. Karper, Paul H.A. Quax
Přispěvatelé: Crystal and Structural Chemistry, Immunofarmacologie van het respiratoire en gastrointestinale systemen, Dep Farmaceutische wetenschappen, Sub Crystal and Structural Chemistry
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Lipopolysaccharides
Male
Pathology
Vascular smooth muscle
Mouse
Gene Expression
Coronary Artery Disease
Biomedische technologie en medicijnen
Cardiovascular
Muscle
Smooth
Vascular
Farmacie/Biofarmaceutische wetenschappen (FARM)
Molecular Cell Biology
Gene expression
Immune Response
Cells
Cultured
Mice
Knockout
Cardiovascular Surgery
Membrane Glycoproteins
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Farmacie(FARM)
Signal transducing adaptor protein
Animal Models
Signaling in Selected Disciplines
Overig medisch onderzoek
Immunohistochemistry
Interventional Cardiology
Innate Immunity
Cell biology
Femoral Artery
Antigens
Surface
Medicine
Immunotherapy
Intracellular
Research Article
Signal Transduction
Neointima
medicine.medical_specialty
Science
Immunology
Hypercholesterolemia
Myocytes
Smooth Muscle
Biology
Immunological Signaling
Model Organisms
Vascular Biology
Antigens
CD
In vivo
Extracellular
medicine
Animals
Humans
Cell Proliferation
Pharmacology
Inflammation
Immunity
Mice
Inbred C57BL
Toll-Like Receptor 4
HEK293 Cells
Solubility
TLR4
Blood Vessels
Clinical Immunology
Surgery
Zdroj: PLoS ONE, Vol 8, Iss 7, p e67923 (2013)
PLoS ONE, 8(7)
PLoS ONE
PLoS ONE, 8(7), e67923
PLoS One, 8(7), 1. Public Library of Science
ISSN: 1932-6203
Popis: Background RP105 (CD180) is TLR4 homologue lacking the intracellular TLR4 signaling domain and acts a TLR accessory molecule and physiological inhibitor of TLR4-signaling. The role of RP105 in vascular remodeling, in particular post-interventional remodeling is unknown. Methods and Results TLR4 and RP105 are expressed on vascular smooth muscle cells (VSMC) as well as in the media of murine femoral artery segments as detected by qPCR and immunohistochemistry. Furthermore, the response to the TLR4 ligand LPS was stronger in VSMC from RP105−/− mice resulting in a higher proliferation rate. In RP105−/− mice femoral artery cuff placement resulted in an increase in neointima formation as compared to WT mice (4982±974 µm2 vs.1947±278 µm2,p = 0.0014). Local LPS application augmented neointima formation in both groups, but in RP105−/− mice this effect was more pronounced (10316±1243 µm2 vs.4208±555 µm2,p = 0.0002), suggesting a functional role for RP105. For additional functional studies, the extracellular domain of murine RP105 was expressed with or without its adaptor protein MD1 and purified. SEC-MALSanalysis showed a functional 2:2 homodimer formation of the RP105-MD1 complex. This protein complex was able to block the TLR4 response in whole blood ex-vivo. In vivo gene transfer of plasmid vectors encoding the extracellular part of RP105 and its adaptor protein MD1 were performed to initiate a stable endogenous soluble protein production. Expression of soluble RP105-MD1 resulted in a significant reduction in neointima formation in hypercholesterolemic mice (2500±573 vs.6581±1894 µm2,p Conclusion RP105 is a potent inhibitor of post-interventional neointima formation.
Databáze: OpenAIRE
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