There is growing experimental evidence to suggest the role of oxidatively modified low-density lipoprotein (LDL) in the initiation and progression of atherosclerosis. The oxidation of lipoprotein moiety causes modification of positively charged lysine residues and results in negative net charge of lipoprotein particles.
Objective: To measure the amount of circulating electronegatively charged LDL particles (LDL-) in plasma of patients with angiographically documented coronary artery disease (CAD).
Methods: Thirty patients were assigned to the study group (CAD+) and 10 patients to the control group (Ctrl). LDL- was quantitated in homogeneous LDL fractions obtained by ultracentrifugation, using ion exchange high performance liquid chromatography. Plasma lipids were measured using enzymatic kits.
Results: The CAD+ group had significantly higher levels of LDL- in the whole LDL fraction (7.66+/-1.92 vs. 5.14+/-0.84%, p=0.0003). Moreover the CAD+ group had significantly higher levels of total cholesterol (255.4+/-35.1 vs. 210.4+/-22.4 mg/dL), LDL cholesterol (154.5+/-26.9 vs. 122.4+/-21.1 mg/dL) and significantly lower levels of high-density lipoprotein (HDL) cholesterol (40.4+/-9.4 vs. 51.0+/-11.5 mg/dL). LDL- remained significantly higher in the CAD+ group after adjustment for total cholesterol, LDL cholesterol and HDL cholesterol (6.3 vs. 5.14% at p=0.0095). There is a trend towards a positive correlation between LDL- levels and LDL cholesterol in the control group (Spearman R=0.55 at p=0.098).
Conclusions: Electronegatively charged LDL appears to be an additional hallmark of coronary artery disease, independently of established lipid risk factors. The trend towards a positive correlation between LDL cholesterol concentration and the level of LDL- in the control group may reflect the susceptibility of LDL cholesterol to autoxidation, Moreover, this may indicate other oxidative mechanisms in coronary artery disease. Nonetheless, further studies assessing the prognostic value of electronegatively charged LDLs are necessary.