Raman spectroscopic investigation of atorvastatin, amlodipine, and both on atherosclerotic plaque development in APOE*3 Leiden transgenic mice.
Raman spectroscopy allows quantitative, non-destructive evaluation of entire, intact atherosclerotic plaques. We quantified the anti-atherosclerotic effects of atorvastatin and amlodipine on progression of atherosclerosis using post-mortem Raman spectroscopic plaque imaging in 28 APOE*3 Leiden transgenic mice who were fed a high fat/high cholesterol diet for 28 weeks. Mice were assigned to a control group receiving the diet alone or to groups that received the diet with either 0.01% w/w atorvastatin, 0.002% w/w amlodipine, or the combination. The entire excised aortic arch was scanned with Raman microspectroscopy for quantitation of the distribution of cholesterol and calcification content. When mice had been treated with atorvastatin, cholesterol accumulation and calcification in the aortic arch was reduced by 91 and 98%, respectively, (both P<0.001). Amlodipine did not reduce the cholesterol content but reduced calcification of the aorta by 69% (P<0.05). The combination of amlodipine and atorvastatin was as effective as atorvastatin alone. This study demonstrates the strong atheroprotective potential of atorvastatin. In addition it is demonstrated that amlodipine reduces mineralization of atherosclerotic plaque. No synergistic effect of the combination of amlodipine and atorvastatin on plaque development is demonstrated. This study encourages Raman spectroscopic evaluations of anti-atherosclerotic drugs in larger animals and humans in vivo.
Department of Cardiology, C5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Sweder W E
SW
van de Poll
Dianne J M
DJ
Delsing
J Wouter
JW
Jukema
Hans M G
HM
Princen
Louis M
LM
Havekes
Gerwin J
GJ
Puppels
Arnoud
A
van der Laarse
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001011:Aorta / Q000473:pathology; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D000069059:Atorvastatin; D002784:Cholesterol / Q000032:analysis*; D004195:Disease Models, Animal; D004357:Drug Synergism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D011758:Pyrroles / Q000627:therapeutic use*; D013059:Spectrum Analysis, Raman / Q000379:methods*
D000959:Antihypertensive Agents; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C052720:apolipoprotein E3 (Leidein); D017311:Amlodipine; D002784:Cholesterol; D000069059:Atorvastatin