J. Lipid Res.
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A more recent version of this article appeared on April 1, 2007

Papers In Press, published online ahead of print January 29, 2007
J. Lipid Res., doi:10.1194/jlr.M600414-JLR200
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Submitted on September 18, 2006
Revised on January 16, 2007
Accepted on January 28, 2007

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

Masako Tabuchi, Katsumi Inoue, Hitomi Usui-Kataoka, Kazuko Kobayashi, Misako Teramoto, Koji Takasugi, Kenichi Shikata, Masahiro Yamamura, Kenji Ando, Keiichiro Nishida, Junko Kasahara, Noriaki Kume, Luis R Lopez, Kazuaki Mitsudo, Masakiyo Nobuyoshi, Tatsuji Yasuda, Toru Kita, Hirofumi Makino, and Eiji Matsuura

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama 700-8558

Corresponding Author: eijimatu{at}md.okayama-u.ac.jp

C-reactive protein (CRP) is one of the strongest independent predictor of cardiovascular disease (CVD). We have previously reported that oxidized LDL (oxLDL) interacts with ß2-glycoprotein I (ß2GPI), implicating oxLDL/ß2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/ß2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/ß2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, non-complexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining co-localized CRP and ß2GPI 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 ICAM-1 and VCAM-1, and oxLDL/ß2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/ß2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/ß2GPI complexes can be distinguished from pyrogenic non-complexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.


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[Abstract] [Full Text] [PDF]


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