LDL OXIDATION IN PATIENTS WITH SEVERE CAROTID ATHEROSCLEROSIS - A STUDY OF IN-VITRO AND IN-VIVO OXIDATION MARKERS

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 CuSO4,. However, vitamin E efficiency was lower (9.6+/-4.2 versus 30.2+/-7.6 mini 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, Cu2+-oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reactivity of the antibodies detected with other oxidatively modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins. Patients with carotid atherosclerosis had an antibody ratio significantly higher than control subjects in regard to anti-oxLDL Ige (1.78+/-0.39 versus 1.05+/-0.3) and IgM (1.98+/-0.83 versus 1.40+/-0.09) and anti-MDA-LDL IgG (2.39+/-0.51 versus 2.04+/-0.11) and IgM (4.18+/-1.89 versus 2.9+/-0.15). The highest titers were found in patients with associated hyperlipidemia and hypertension, alone or in combination. On the other hand, the anti-MDA-HSA antibody titer did not differ between the two groups of patients investigated. These data indicate that patients with severe carotid atherosclerosis specifically develop autoantibodies against oxidatively modified LDL and, despite an apparently ''normal'' oxidation profile in vitro, provide support for the occurrence of an enhanced LDL oxidation in vivo.