The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis.
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.
Tabuchi
Masako
M
Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Inoue
Katsumi
K
Usui-Kataoka
Hitomi
H
Kobayashi
Kazuko
K
Teramoto
Misako
M
Takasugi
Koji
K
Shikata
Kenichi
K
Yamamura
Masahiro
M
Ando
Kenji
K
Nishida
Keiichiro
K
Kasahara
Junko
J
Kume
Noriaki
N
Lopez
Luis R
LR
Mitsudo
Kazuaki
K
Nobuyoshi
Masakiyo
M
Yasuda
Tatsuji
T
Kita
Toru
T
Makino
Hirofumi
H
Matsuura
Eiji
E
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
D015415:Biomarkers; D008077:Lipoproteins, LDL; D046912:Multiprotein Complexes; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein