LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

Abstract

Among the various risk factors involved in the development and progression of carotid atherosclerosis, the oxidation of LDL has been proposed to play a relevant role. LDL oxidation has been investigated in 94 patients with severe carotid atherosclerosis undergoing elective carotid artery endarterectomy and in 42 matched control subjects. LDL oxidation was evaluated in all patients as (1) the susceptibility to in vitro oxidation, (2) vitamin E concentration and its efficiency in LDL, and (3) the presence of autoantibodies against oxidatively modified lipoprotein to monitor the occurrence of the oxidative processes taking place in vivo. No difference was detected between control subjects and patients concerning vitamin E concentration and the kinetics of conjugated diene formation in isolated LDL exposed to CuSO 4 . However, vitamin E efficiency was lower (9.6±4.2 versus 30.2±7.6 min/ nmol vitamin E) and the duration of the vitamin E-independent lag phase was longer (105.5±16.5 versus 58± 11.8 minutes) in the patient group. Autoantibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu 2+ -oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reactivity of the antibodies detected with other C arotid atherosclerosis, ranging from intima-media thickening to the appearance of more advanced lesions such as fibrotic and complicated plaques, affects about 25% of the whole population.

Autoimmunity and oxidatively modified autoantigens

“…The presence of antibodies against ox-LDL or malondialdehyde-LDL in atherosclerotic plaques and oxidation-specific antigens on surface of apoptotic cells have been demonstrated by numerous investigators The presence of anti-oxidized LDL is associated with more rapid progression of atherosclerosis. Antigens modified by oxidative by-products induce immune responses in alcoholic liver disease [9,10].…”

“…The use of the Schiff base-forming agent tucaresol, in addition, during immunization with protein antigen increased T cell dependent immune response. Direct modification of protein antigen has been shown to be required for the enhancement of the immune response [6,[9][10][11][12].…”

Atherogenesis and the humoral immune response to modified lipoproteins

“…The results of these studies were rather disappointing, because the results were often conflicting and failed to produce a clear cut indication of the clinical value of modified lipoprotein antibody assays as biomarkers for the development and/or progression of atherosclerosis. While some groups reported a positive correlation between the levels of oxLDL antibodies and different endpoints considered as evidence of atherosclerotic vascular disease, such as progression of carotid atherosclerosis or risk for the future development of myocardial infarction [21][22][23][24][25][26][27], others failed to show such correlation or showed an inverse correlation [28][29][30][31][32][33][34][35][36][37][38].…”

Association of non-HDL cholesterol with subclinical atherosclerosis in HIV-positive patients

“…Results were expressed in arbitrary units (AU); v) Measurement of anti MDA-modified LDL auto-antibodies (MDA-LDL Ab) was performed using an enzyme linked immunosorbent assay 24 . Briefly, antigen was prepared by incubation of isolated LDL for 3 hours at 37°C with MDA.…”