[Calcium channel blockers inhibit human low-density lipoprotein peroxidation induced by oxygen free radicals in vitro].
Previous studies have shown that calcium-antagonists may reduce the development of experimental atherosclerosis, and that nifedipine may slow progression of coronary atherosclerosis in man. The mechanisms responsible for this effect are still unclear. It has been recently proposed that oxygen-free radicals can induce peroxidation of human low-density lipoproteins (LDL), and that peroxidized LDL may be an atherogenic stimulus. Chemical modified LDL are internalized by macrophages via specific cell surface receptor that was termed the scavenger receptor, and could induce foam cells transformation in vivo. Previous studies on other systems have shown that calcium-antagonists may effectively inhibit oxygen radical-induced lipid peroxidation. These drugs, though differing widely in their chemical structure, are lipophilic to various degrees and presumably would concentrate in the lipid domain of the phospholipid-rich membranes. Therefore, the aim of the present study was to investigate whether calcium-channel blockers may reduce human LDL peroxidation. Purified human LDL were exposed to oxygen radicals generated by xanthine-xanthine oxidase (18 hours) after a pre-incubation (30 min) in presence of different concentrations of nifedipine, diltiazem and verapamil. Peroxidation was measured from malonyldialdehyde production. The results show that calcium-antagonists prevent LDL peroxidation. Thus, calcium-antagonists may reduce peroxidation of human LDL in vitro, at clinically relevant concentrations. These data suggest that reduced formation of atherogenic peroxidized LDL may be an additional mechanism for the anti-atherosclerotic effects of calcium-antagonists in vivo.
Napoli
C
C
Cattedra di Cardiologia, II Facoltà di Medicina e Chirurgia, Università degli Studi Federico II, Napoli.
Ambrosio
G
G
Palumbo
G
G
Chiariello
P
P
Chiariello
M
M
D001161:Arteriosclerosis / Q000188:drug therapy* / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
D002121:Calcium Channel Blockers; D008077:Lipoproteins, LDL
I calcioantagonisti inibiscono la perossidazione delle lipoproteine umane a bassa densità indotta dai radicali liberi dell'ossigeno in vitro.