Title
Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice
Author
Delsing, D.J.M.
Jukema, J.W.
van de Wiel, M.A.
Emeis, J.J.
van der Laarse, A.
Havekes, L.M.
Princen, H.M.G.
Gaubius Instituut TNO
Publication year
2003
Abstract
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.
Subject
Biology
Biomedical Research
Atherosclerosis
Calcification
Calcium antagonists
Inflammation
Statins
Amlodipine
Atorvastatin
Hydroxymethylglutaryl coenzyme A reductase inhibitor
Very low density lipoprotein cholesterol
Animal model
Animal tissue
Aorta root
Cholesterol blood level
Cholesterol diet
Controlled study
Drug effect
Inflammation
Mouse
Nonhuman
Amlodipine
Animals
Aorta, Thoracic
Apolipoprotein E3
Apolipoproteins E
Arteriosclerosis
Blood Pressure
Calcium Channel Blockers
Cholesterol
Cholesterol, Dietary
Drug Therapy, Combination
Female
Heptanoic Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mice
Mice, Transgenic
Pyrroles
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DOI
https://doi.org/10.1097/00005344-200307000-00010
TNO identifier
237159
ISSN
0160-2446
Source
Journal of Cardiovascular Pharmacology, 42 (1), 63-70
Document type
article