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.