MALONDIALDEHYDE-MODIFIED LOW-DENSITY LIPOPROTEINS IN PATIENTS WITH ATHEROSCLEROTIC DISEASE

The murine monoclonal antibody mAb-1H11 raised against malondialdehyde (MDA)-modified LDL, was used to detect cross-reacting material in hum an atheromatous tissue and in plasma, MDA-modified LDL levels in plasm a were 0.19+/-0.02 mg/dl (mean+/-SEM) in 44 control subjects, 0.24+/-0 .02 mg/dl in 15 patients with chronic stable angina pectoris (P = NS v s LDL cholesterol matched controls), 1.4+/-0.1 mg/dl in 60 patients wi th acute myocardial infarction (P < 0.001 vs controls), and 0.86+/-0.1 1 mg/dl in 22 patients with carotid atherosclerosis (P < 0.001 vs cont rols), Modified LDL, isolated from pooled LDL of 10 patients, showed a higher electrophoretic mobility on agarose gels, a higher content of thiobarbituric acid reactive substances, and a higher cholesterol/prot ein ratio than native LDL and had a similar reactivity (antigen/protei n ratio) in the assay as the in vitro MDA-modified LDL used for calibr ation, Its apo B-100 moiety was not fragmented, Uptake of this modifie d LDL by macrophages resulted in foam cell generation, In conclusion, elevated plasma levels of atherogenic MDA-modified LDL may be a marker for unstable atherosclerotic cardiovascular disease.