Influence of acetylsalicylic acid on oxidation of native and glycated low-density lipoprotein

It is generally accepted that oxidation of low-density lipoproteins (LDL) i s a causal factor in the development of atherosclerosis. Non-enzymatic glyc osylation of LDL, i.e. "glycation", plays a central role in late complicati ons of diabetes mellitus and may initiate and/or accelerate the oxidation p rocess. Therefore, the inhibition of this processes is of major therapeutic relevance. The influence of acetylsalicylic acid (ASA) on the oxidation of native and glycated LDL was studied in vitro. LDL (0.25 mg protein/ml) was oxidatively modified with 5.0 mu M CuSO4. Only at "supratherapeutical" ASA concentrations in the range 0.06-2.0 mg/ml we found a significant concentr ation-dependent inhibition of LDL oxidation both for native and glycated LD L, which was from 0.2 mg/ml upwards significantly more marked for native LD L than for glycated LDL. The maximal inhibitory effect occurred at 2.0 mg/m l with 89.6% inhibition of LDL-oxidation for native LDL and 64.4% for glyca ted LDL. At 0.2 mg/ml ASA the respective inhibitory values were 38.5% and 3 1.0%. For glycated LDL the ASA doses of maximal- and approximately 50%-inhi bition, as found for native LDL, were chosen to investigate the inhibitory effect on 2,4,8 and 24 hours oxidation of glycated LDL to monitor the time- dependency of inhibition by ASA. This revealed that ASA only delayed, not p ermanently inhibited LDL oxidation.