Oxidized LDL in Carotid Plaques and Plasma Associates With Plaque Instability

OBJECTIVE: Oxidation of LDL plays a significant pathogenic role in atherosclerosis. In this study, we attempted to clarify the correlation between the morphology of human atherosclerotic plaques and the oxidized LDL (OxLDL) levels in plasma and carotid plaques. METHODS AND RESULTS: OxLDL levels (ng/microg apolipoprotein B) in plasma and carotid plaques from 44 patients undergoing carotid endarterectomy and OxLDL levels in 17 control plasma and 9 normal intima samples were determined by a sandwich ELISA by using specific antibodies against OxLDL (DLH3) and apolipoprotein B. The plaques were immunohistochemically classified as macrophage (Mphi)-rich and Mphi-poor. In paired samples from individual patients, plaque OxLDL was nearly 70 times higher than plasma OxLDL (mean+/-SEM, 11.9+/-1.7 vs 0.18+/-0.01 ng/microg apoB, P<0.0001). The OxLDL level was significantly higher in Mphi-rich- than Mphi-poor plaques (19.6+/-2.8 vs 5.50+/-0.77 ng/microg apoB, P<0.0001) and corresponded with DLH3 antigen positivity of the plaques. In patients with Mphi-rich plaques, plasma OxLDL was significantly higher than in the controls (0.20+/-0.02 vs 0.13+/-0.01 ng/microg apoB, P=0.02). CONCLUSIONS: Our results suggest that LDL undergoes further oxidation in plaques, and that high plasma and plaque levels of OxLDL are correlated with the vulnerability to rupture of atherosclerotic lesions.