Proteoglycan 4 regulates macrophage function without altering atherosclerotic lesion formation in a murine bone marrow-specific deletion model

Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was invest...

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Veröffentlicht in:	Atherosclerosis 2018-07, Vol.274, p.120-127
Hauptverfasser:	Nahon, Joya E., Hoekstra, Menno, Havik, Stefan R., Van Santbrink, Peter J., Dallinga-Thie, Geesje M., Kuivenhoven, Jan-Albert, Geerling, Janine J., Van Eck, Miranda
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Atherosclerosis Atherosclerosis - genetics Atherosclerosis - metabolism Atherosclerosis - pathology ATP Binding Cassette Transporter 1 - metabolism Bone Marrow Cells - metabolism Bone Marrow Cells - pathology Bone Marrow Transplantation Carotid Arteries - metabolism Carotid Arteries - pathology Carotid Artery Diseases - genetics Carotid Artery Diseases - metabolism Carotid Artery Diseases - pathology Cells, Cultured Cholesterol - metabolism Disease Models, Animal Foam Cells - drug effects Foam Cells - metabolism Foam Cells - pathology Foam Cells - transplantation Humans Inflammation Mediators - metabolism Lipopolysaccharides - pharmacology Macrophage function Macrophages, Peritoneal - drug effects Macrophages, Peritoneal - metabolism Macrophages, Peritoneal - pathology Macrophages, Peritoneal - transplantation Male Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout, ApoE Phenotype Plaque, Atherosclerotic Proteoglycan 4 Proteoglycans Proteoglycans - deficiency Proteoglycans - genetics Proteoglycans - metabolism Scavenger Receptors, Class B - metabolism Tumor Necrosis Factor-alpha - metabolism
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Zusammenfassung:	Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was investigated. The presence and localization of Prg4 was studied in atherosclerotic lesions. Furthermore, the effect of Prg4 deficiency on macrophage foam cell formation, cholesterol efflux and lipopolysaccharide (LPS) response was determined. Finally, susceptibility for atherosclerotic lesion formation was investigated in bone marrow-specific Prg4 knockout (KO) mice. Prg4 mRNA expression was induced 91-fold (p
ISSN:	0021-9150 1879-1484
DOI:	10.1016/j.atherosclerosis.2018.05.008