Raman spectroscopic evaluation of the effects of diet and lipid-lowering therapy on atherosclerotic plaque development in mice

Quantitative characterization of atherosclerotic plaque composition with st andard histopathological methods remains limited to sectioned plaques. Rama n spectroscopy enables nondestructive quantification of atherosclerotic pla que composition. We used Raman spectroscopy to study the effects of diet an d 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, an d 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 mon ths, Raman spectroscopy showed good correlation between cholesterol accumul ation and total serum cholesterol exposure (r approximate to0.87, 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 stud y the size and distribution of depositions of cholesterol and calcification in A-POE*3-Leiden transgenic mice. This study encourages Raman spectroscop y for the quantitative investigation of atherosclerosis and lipid-lowering therapy in larger animals or humans in vivo.