title: F(ab')2fragments of anti-oxidized LDL IgG attenuate vascular inflammation and atherogenesis in diabetic LDL receptor-deficient mice.
abstract: Considerable evidence is available supporting the atherogenic role of immune complexes (IC) formed by modified forms of LDL and their corresponding antibodies in humans and other species. In this study, we assessed the effect of IgG F(ab')2fragments of murine anti-mouse oxLDL, which binds oxLDL forming IC that cannot interact with Fcγ receptors, on the development of atherosclerosis in diabetic LDL receptor-deficient (LDLR-/-) mice. Immunohistochemical study showed that treatment with the F(ab')2fragments for 8weeks significantly reduced the content of macrophages and interleukin 6 expression in atherosclerotic lesions. Furthermore, histological study showed that treatment with the same F(ab')2fragments significantly reduced atherosclerotic lesions in diabetic LDLR-/- mice. Taken together, this study demonstrated for the first time that F(ab')2fragments of anti-oxLDL IgG inhibited vascular inflammation and atherogenesis in diabetic LDLR-/- mice and uncovered a possible new avenue for therapy in patients at high risk to progress to cardiovascular complications.
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, United States.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, United States.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, United States; Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, United States; Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, United States.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, United States. Electronic address: virellag@musc.edu.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Virella
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000276:immunology*; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D001323:Autoantibodies; C052643:F(ab')2 receptor; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D011971:Receptors, Immunologic; D011973:Receptors, LDL; C577686:interleukin-6, mouse; C099252:oxidized low density lipoprotein
keywords: Atherosclerosis; Inflammation; Low-density lipoprotein; Oxidized LDL; Oxidized LDL antibody; Phagocytosis