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 progres sion of carotid atherosclerosis, the oxidation of LDL has been propose d to play a relevant role. LDL oxidation has been investigated in 94 p atients with severe carotid atherosclerosis undergoing elective caroti d artery endarterectomy and in 42 matched control subjects. LDL oxidat ion was evaluated in all patients as (1) the susceptibility to in vitr o oxidation, (2) vitamin E concentration and its efficiency in LDL, an d (3) the presence of autoantibodies against oxidatively modified lipo protein to monitor the occurrence of the oxidative processes taking pl ace in vivo. No difference was detected between control subjects and p atients concerning vitamin E concentration and the kinetics of conjuga ted diene formation in isolated LDL exposed to CuSO4,. However, vitami n E efficiency was lower (9.6+/-4.2 versus 30.2+/-7.6 mini nmol vitami n E) and the duration of the vitamin E-independent lag phase was longe r (105.5+/-16.5 versus 58+/-11.8 minutes) in the patient group. Autoan tibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu2+-oxidized LDL (oxLDL), or malond ialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reac tivity of the antibodies detected with other oxidatively modified prot eins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed. The antibody titer was calculated as the ratio of anti bodies against modified versus native proteins. Patients with carotid atherosclerosis had an antibody ratio significantly higher than contro l 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 patie nts investigated. These data indicate that patients with severe caroti d atherosclerosis specifically develop autoantibodies against oxidativ ely modified LDL and, despite an apparently ''normal'' oxidation profi le in vitro, provide support for the occurrence of an enhanced LDL oxi dation in vivo.