Effects of amlodipine, atorvastatin and combination of both on advanced atherosclerotic plaque in APOE*3-Leiden transgenic mice.
Combined treatment of statins and calcium channel blockers has been suggested to be superior to statin therapy alone. We quantified the anti-atherosclerotic potential of amlodipine, atorvastatin and their combination on existing atherosclerotic plaques in the aorta of APOE*3-Leiden transgenic mice. Sixty-two mice were fed a high cholesterol containing diet for 18 weeks. A subgroup of 10 mice was then killed. All other mice received the diet for another 18 weeks, alone (late control group), along with 0.01% atorvastatin, 0.002% w/w amlodipine, or their combination (all groups, n = 13). Atherosclerotic lesions, collagen content and monocyte adherence were quantified using standard histology (aortic root). Raman spectroscopy was used to quantify the content of cholesterol and calcification (aortic arch). Compared to the late control group, treatment with amlodipine, atorvastatin or the combination, reduced atherosclerostic lesion area by, respectively, 25%, 39% and 46% in the aortic root (P < 0.01) and by 53%, 55% and 60% in the aortic arch (P < 0.05). Atorvastatin, but not amlodipine reduced the adherence of monocytes in the intima. Lesion severity and plaque contents of collagen, cholesterol and calcification were equal for all treatment groups. Neither treatment resulted in regression of atherosclerotic plaque size. In conclusion, both atorvastatin and amlodipine significantly retard the progression of existing atherosclerotic lesions. No additive effect of the combination of amlodipine and atorvastatin could be observed in this study.
van de Poll
Sweder W E
SW
Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Delsing
Dianne J M
DJ
Wouter Jukema
J
J
Princen
Hans M G
HM
Havekes
Louis M
LM
Puppels
Gerwin J
GJ
van der Laarse
Arnoud
A
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000188:drug therapy*; D000069059:Atorvastatin; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011758:Pyrroles / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D002121:Calcium Channel Blockers; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D017311:Amlodipine; D002784:Cholesterol; D000069059:Atorvastatin