Oxysterol profiles of normal human arteries, fatty streaks and advanced lesions

Objective: Human atherosclerotic lesions of different stages have quantitat ive differences in cholesterol and oxysterol content, but information on th e oxysterol profile in fatty streaks is limited. This study aims to provide more detailed oxysterol quantification in human fatty streaks, as well as normal aorta and advanced lesions. Methods: A newly adapted method was used, including oxysterol purification by means of a silica cartridge; and it was ensured that artifactual oxyster ol formation was kept to a minimum. Cholesterol and oxysterols were estimat ed by GC and identification confirmed by GC-MS in samples of normal human a rterial intima, intima with near-confluent fatty streaks and advanced lesio ns, in necropsy samples. Results: The oxysterols 7 alpha -hydroxycholesterol, cholesterol-5 beta, 6 beta -epoxide, cholesterol-5 alpha, 6 alpha -epoxide, 7 beta -hydroxycholes terol, 7-ketocholesterol and 27-hydroxycholesterol (formerly known as 26-hy droxycholesterol) were found in all the lesions, but were at most very low in the normal aorta, both when related to wet weight and when related to ch olesterol. Most components of the normal artery showed some crosscorrelatio n on linear regression analysis, but crosscorrelations were weaker in the f atty streaks and advanced lesions. However, in fatty streak there was a mar ked positive correlation between 27-hydroxycholesterol and cholesterol. Conclusion: The findings confirm that oxysterols are present in fatty strea ks and advanced lesions and may arise from different cholesterol oxidation mechanisms, including free radical-mediated oxidation and enzymatic oxidati on.