title: Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice.
abstract: Phosphorylcholine (PC) headgroup is one of the neoantigens exposed by LDL oxidation that can elicit an immune response. Active immunization with Streptococcus pneumoniae, which bears PC on its cell wall, reduced atherosclerosis in hypercholesterolemic mice and this effect was attributed to an immune response to PC. In this study we tested the hypothesis that passive immunization with a monoclonal anti-PC IgM antibody can be athero-protective in a murine model of native aortic and vein graft atherosclerosis. Inferior vena cava from 16-week-old donor male apoE-null mice was grafted into right carotid artery of age-matched male recipient apoE-null mice. Anti-PC IgM titers were evaluated before and 4 weeks after surgery. For the immunization protocol, a separate group of mice received weekly intraperitoneal injection of monoclonal anti-PC IgM (400 microg) for 4 weeks, starting the day of surgery. Controls received PBS or pooled polyclonal IgM. Anti-PC IgM titres significantly increased at 4 weeks following surgery. Passive immunization with anti-PC IgM reduced vein graft plaque size and neointimal thickness resulting in a larger luminal area; in addition immunization reduced the inflammatory cell content of the plaques. There was no significant effect on the established native aortic atherosclerotic lesions. Immunization did not affect circulating cholesterol levels. Taken together our data suggest that passive immunization with anti-PC IgM significantly reduces vein graft lesion size with less inflammatory phenotype without affecting cholesterol levels, indicating an athero-protective immune response to PC. Lack of effect on established native aortic lesions may have been due to short duration of therapy and/or reduced efficacy in established lesions as compared to evolving lesions of vein graft atherosclerosis.
authors.affiliation: Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Faria-Neto
authors.forename: Kuang-Yuh
authors.initials: KY
authors.lastname: Chyu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.forename: Paul C
authors.initials: PC
authors.lastname: Dimayuga
authors.forename: Carmel
authors.initials: C
authors.lastname: Ferreira
authors.forename: Juliana
authors.initials: J
authors.lastname: Yano
authors.forename: Bojan
authors.initials: B
authors.lastname: Cercek
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D002339:Carotid Arteries / Q000601:surgery; D004195:Disease Models, Animal; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007116:Immunization, Passive / Q000379:methods*; D007075:Immunoglobulin M / Q000276:immunology*; D008297:Male; D051379:Mice; D010767:Phosphorylcholine / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D014682:Vena Cava, Inferior / Q000637:transplantation
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D007075:Immunoglobulin M; D010767:Phosphorylcholine