Antiatherosclerotic and antiatherogenic effects of a calcium antagonist plus statin combination: amlodipine and lovastatin.
Recently, the Regression Growth Evaluation Statin Study (REGRESS) demonstrated the synergistic, antiatherogenic effect of lipid-lowering therapy with pravastatin in combination with calcium antagonists. This combination retarded the progression of stenosis and reduced the number of new lesions more effectively than did statin therapy alone. In the present study, our objective was to elucidate the mechanism of this more pronounced effect of the statin-calcium antagonist combination on the atherosclerotic lesion. Smooth muscle cells cultured from the subendothelial intima of the human aorta were incubated with whole blood serum or with low-density lipoprotein (LDL) taken from patients cotreated with lovastatin and amlodipine. Serum added to the cells cultured from the atherosclerotic lesion reduced cell cholesterol. Such an antiatherosclerotic effect of cotreatment with amlodipine-lovastatin was revealed in this study and was more pronounced than the effect of treatment with either amlodipine or lovastatin alone. LDL isolated from atherogenic plasma stimulated cell cholesterol accumulation. Treatment with amlodipine alone and the amlodipine-lovastatin combination ameliorated the atherogenic effect of LDL. As compared with amlodipine alone, the combination demonstrated a considerably higher antiatherogenic effect on LDL atherogenicity. Amlodipine-lovastatin cotreatment increased sialic acid and decreased the susceptibility of LDL to oxidation more effectively than amlodipine alone. In addition, combination therapy reduced the LDL negative charge, while amlodipine alone was impotent. These findings may serve as an explanation of the more pronounced antiatherogenic effect at the lipoprotein level of amlodipine-lovastatin combined therapy compared with amlodipine therapy alone.
Orekhov
A N
AN
Institute of Experimental Cardiology, Cardiology Research Center, Institute for Atherosclerosis Research Ltd., Moscow, Russia.
Tertov
V V
VV
Sobenin
I A
IA
Akhmedzhanov
N M
NM
Pivovarova
E M
EM
D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001011:Aorta; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003470:Culture Media; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood; D008148:Lovastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D002121:Calcium Channel Blockers; D003470:Culture Media; D008077:Lipoproteins, LDL; D017311:Amlodipine; D002784:Cholesterol; D008148:Lovastatin