Anti-atherosclerotic effect of amlodipine, alone and in combination with atorvastatin, in APOE*3-Leiden/hCRP transgenic mice.
We investigated the pleiotropic effects of a calcium antagonist (amlodipine) on early atherosclerosis development in the presence and absence of an HMG-CoA-reductase inhibitor (atorvastatin) in apolipoprotein E*3-Leiden/human C-reactive protein (E3L/CRP) transgenic mice. Male E3L/CRP transgenic mice were fed a cholesterol-containing diet either with or without amlodipine and/or atorvastatin. After 31 weeks, atherosclerosis in the aortic root area was quantified. Treatment with amlodipine did not significantly lower blood pressure, but resulted in a 43% reduction (P < 0.03) of lesion area as compared with the untreated group. Treatment with atorvastatin resulted in an 80% reduction of lesion area as compared with the untreated group (P < 0.001). Combined treatment with amlodipine and atorvastatin decreased the lesion area by 93%, significantly more than either treatment alone (P < 0.008). Plasma C-reactive protein levels were mildly elevated, on average 10 +/- 6 mg/L, and did not differ between groups, neither on baseline nor during treatment. Treatment with amlodipine, independently of blood pressure lowering, reduced atherosclerosis development in E3L/CRP mice. Atorvastatin had a strong anti-atherosclerotic effect, whereas co-treatment with amlodipine enhanced this effect significantly. Plasma C-reactive protein levels were not affected by any of the three treatments.
Trion
Astrid
A
Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands.
de Maat
Moniek
M
Jukema
Wouter
W
Maas
Annemarie
A
Offerman
Erik
E
Havekes
Louis
L
Szalai
Alex
A
van der Laarse
Arnoud
A
Princen
Hans
H
Emeis
Jef
J
D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000502:physiology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000150:complications*; D051379:Mice; D008822:Mice, Transgenic; D011758:Pyrroles / Q000008:administration & dosage*; D000685:Serum Amyloid A Protein / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000685:Serum Amyloid A Protein; D014841:von Willebrand Factor; D017311:Amlodipine; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin