Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice
article
This study was designed to investigate the potential antiatherosclerotic effects of the calcium antagonist amlodipine as compared with the HMG-CoA reductase inhibitor atorvastatin and the combination of both in ApoE*3-Leiden transgenic mice. Four groups of 15 ApoE*3-Leiden mice were put on a high-cholesterol diet. One group received 0.002% (wt/wt) amlodipine in the diet, which had no effect on plasma cholesterol levels. Another group received 0.01% (wt/wt) atorvastatin, resulting in a decrease of plasma cholesterol by 50% by a reduction in very low density lipoprotein production. The combination group received both amlodipine and atorvastatin. After 28 weeks, atherosclerosis in the aortic root was quantified. Treatment with amlodipine had no significant effect on atherosclerotic lesion area, whereas atorvastatin markedly reduced atherosclerosis by 77% compared with the control group. Atorvastatin also reduced inflammation markers. The combination of amlodipine and atorvastatin tended to reduce lesion area by 61% compared with the atorvastatinonly group; however, this effect did not reach statistical significance. Amlodipine treatment significantly reduced calcification in the lesions, whereas atorvastatin alone had no effect. The combination of amlodipine and atorvastatin resulted in a near absence of calcium deposits in the lesions. This study demonstrates that amlodipine treatment alone does not significantly reduce atherosclerotic lesion development. Atorvastatin was shown to have strong antiatherosclerotic effects, and cotreatment with amlodipine may potentiate the antiatherosclerotic effect of atorvastatin.
Topics
Biomedical ResearchAtherosclerosisCalcificationCalcium antagonistsInflammationStatinsAmlodipineAtorvastatinHydroxymethylglutaryl coenzyme A reductase inhibitorVery low density lipoprotein cholesterolAnimal modelAnimal tissueAorta rootCholesterol blood levelCholesterol dietControlled studyDrug effectInflammationMouseNonhumanAmlodipineAnimalsAorta, ThoracicApolipoprotein E3Apolipoproteins EArteriosclerosisBlood PressureCalcium Channel BlockersCholesterolCholesterol, DietaryDrug Therapy, CombinationFemaleHeptanoic AcidsHydroxymethylglutaryl-CoA Reductase InhibitorsMiceMice, TransgenicPyrroles
TNO Identifier
237159
ISSN
01602446
Source
Journal of Cardiovascular Pharmacology, 42(1), pp. 63-70.
Pages
63-70
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