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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1630.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Raman Spectroscopic Evaluation of the Effects of Diet and Lipid-Lowering Therapy on Atherosclerotic Plaque Development in Mice

Sweder W.E. van de Poll; Tjeerd J. Römer; Oscar L. Volger; Dianne J.M. Delsing; Tom C. Bakker Schut; Hans M.G. Princen; Louis M. Havekes; J. Wouter Jukema; Arnoud van der Laarse; Gerwin J. Puppels

From the Department of Cardiology (S.W.E.v.d.P., T.J.R., J.W.J., A.v.d.L.), Leiden University Medical Center, Leiden; the Interuniversity Cardiology Institute of the Netherlands (S.W.E.v.d.P., A.v.d.L.), Utrecht; the Gaubius Laboratory (O.L.V., H.M.G.P., L.M.H.), TNO-PG, Leiden; and the Laboratory for Intensive Care Research and Optical Spectroscopy (S.W.E.v.d.P., T.C.B.S., G.J.P.), Erasmus University, Rotterdam, the Netherlands.

Correspondence to Gerwin J. Puppels, PhD, Laboratory for Intensive Care Research and Optical Spectroscopy, Erasmus University Rotterdam and University Hospital Rotterdam "Dijkzigt," Surgery 10 M, Dr Molenwaterplein 40, 3015 GD Rotterdam, The Netherlands. E-mail puppels{at}hlkd.azr.nl

Abstract—— Quantitative characterization of atherosclerotic plaque composition with standard histopathological methods remains limited to sectioned plaques. Raman spectroscopy enables nondestructive quantification of atherosclerotic plaque composition. We used Raman spectroscopy to study the effects of diet and lipid-lowering therapy on plaque development in apolipoprotein (APO) E*3-Leiden transgenic mice. Raman spectra were obtained over the full width and entire length of the ascending aorta and aortic arch. Spectra were modeled to calculate the relative dry weights of cholesterol and calcium salts, and quantitative maps of their distribution were created. In male mice (n=20) that received a high-fat/high-cholesterol (HFC) diet for 0, 2, 4, or 6 months, Raman spectroscopy showed good correlation between cholesterol accumulation and total serum cholesterol exposure (r0.87, P<0.001). In female mice (n=10) that were assigned to an HFC diet, with or without 0.01% atorvastatin, a strong reduction in cholesterol accumulation (57%) and calcium salts (97%) (P<0.01) was demonstrated in the atorvastatin-treated group. In conclusion, Raman spectroscopy can be used to quantitatively study the size and distribution of depositions of cholesterol and calcification in APOE*3-Leiden transgenic mice. This study encourages Raman spectroscopy for the quantitative investigation of atherosclerosis and lipid-lowering therapy in larger animals or humans in vivo.

Key Words: atherosclerosis • Raman spectroscopy • cholesterol • calcification • lipid-lowering treatment

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