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 b2-glycoprotein I (b2GPI), implicating oxLDL/b2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/b2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/b2GPI 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 b2GPI 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/b2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/b2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/b2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.-Tabuchi, M., K.

Ezetimibe Ameliorates Metabolic Disorders and Microalbuminuria in Patients with Hypercholesterolemia

“…It has been shown that nonalcoholic fatty liver disease, including hepatic steatosis, is closely related via enhanced inflammation to insulin resistance, metabolic syndrome, and cardiovascular disease [21][22][23][24] . Tabuchi et al 25) reported that ezetimibe inhibits the absorption of oxidized cholesterol and its deposition in the liver. Using a rat model of metabolic syndrome, Deushi et al 26) documented that ezetimibe improved liver steatosis and insulin resistance by decreasing hepatic lipid deposition and fibrosis of the liver and effectively reduced systemic dyslipidemia.…”

Oxidized LDL: Diversity, Patterns of Recognition, and Pathophysiology

“…. The generation of CRP=OxLDL= b2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia (277). Immunohistochemistry staining co-localized OxLDL, b2GPI, and CRP in carotid artery plaques (277).…”

Measurement of Plasma Oxidized Low-Density Lipoprotein and its Clinical Implications

“…A couple such as C-reactive protein (CRP), soluble forms of lectin-type OxLDL receptor-1, or small dense LDL are of interest, because CRP and sLOX-1 could bind to OxLDL and small dense LDL is thought to be susceptible to oxidative modification [56][57][58] . It is certainly necessary to correlae plasma OxLDL levels and these other markers and their clinical relevance in the future.…”