Calcium-channel blockers inhibit human low-density lipoprotein oxidation by oxygen radicals.
Previous studies have shown that calcium channel blockers may reduce the development of experimental atherosclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may be an atherogenic stimulus. Previous studies in other systems have shown that calcium channel blockers may effectively inhibit oxygen radical-induced lipid peroxidation in vitro. Thus, the aim of the present study was to investigate whether calcium channel blockers may also reduce LDL modifications induced by oxygen radicals. Isolated human LDL were exposed to oxygen radicals generated by CuSO4 (10 microM for 18 hours) after a 30 minute pre-incubation with different concentrations (1-100 microM) of nifedipine, diltiazem, and verapamil. Lipid peroxidation was measured from malonyldihaldehyde (MDA) production. Oxygen radical-induced damage on apolipoprotein-B100 was evaluated by acrylamide and agarose gel electrophoresis. Calcium channel blockers dose-dependently prevented oxidation of both the lipid and protein components of LDL. MDA formation was reduced in LDL pre-incubated with calcium antagonists before exposure to oxygen radicals (% MDA inhibition was 89.8 +/- 6.9 with 30 microM nifedipine, 68.6 +/- 4.9 with 30 microM verapamil, and 65.6 +/- 7.1 with 30 microM diltiazem; p < 0.01 vs. controls). Similarly, apolipoprotein-B100 integrity was preserved against oxygen radical attack in the presence of calcium antagonists. Thus, calcium channel blockers reduce the oxidation of human LDL in vitro. These data suggest that reduced formation of atherogenic oxidized LDL may be an additional mechanism for the antiatherosclerotic effects of calcium channel blockers in vivo.
Napoli
C
C
Division of Cardiology, Federico II School of Medicine, University of Naples, Italy.
Chiariello
M
M
Palumbo
G
G
Ambrosio
G
G
D000704:Analysis of Variance; D001161:Arteriosclerosis / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015180:Electrophoresis, Gel, Two-Dimensional; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen
D002121:Calcium Channel Blockers; D005609:Free Radicals; D008077:Lipoproteins, LDL; D010100:Oxygen