title: The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis.
abstract: C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), implicating oxLDL/beta2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/beta2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/beta2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/beta2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.
authors.affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Tabuchi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Inoue
authors.forename: Hitomi
authors.initials: H
authors.lastname: Usui-Kataoka
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Misako
authors.initials: M
authors.lastname: Teramoto
authors.forename: Koji
authors.initials: K
authors.lastname: Takasugi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shikata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Ando
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Junko
authors.initials: J
authors.lastname: Kasahara
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kume
authors.forename: Luis R
authors.initials: LR
authors.lastname: Lopez
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mitsudo
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Nobuyoshi
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Yasuda
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
mesh_terms: D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis* / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000097:blood*; D010084:Oxidation-Reduction; D011237:Predictive Value of Tests; D053482:beta 2-Glycoprotein I / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008077:Lipoproteins, LDL; D046912:Multiprotein Complexes; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein