LOCALIZATION OF STEROL 27-HYDROXYLASE IMMUNO-REACTIVITY IN HUMAN ATHEROSCLEROTIC PLAQUES

It has recently been shown that extrahepatic cells can eliminate intra cellular cholesterol by enzymatic conversion into 77-hydroxy-cholester ol and 3 beta-hydroxy-5-cholestenoic acid. Using immunohistochemical m ethods, we studied the presence of the enzyme responsible for these co nversions, sterol 27-hydroxylase, in human carotid atherosclerotic pla ques. All plaques examined were found to contain sterol 27-hydroxylase immune-reactive cells. While some endothelial cells stained for stero l 27-hydroxylase, the majority of the immunoreactive cells co-localize d with macrophages. Accumulation of sterol 27-hydroxylase-positive cel ls were often observed in macrophage-rich core regions of complicated lesions. High concentrations of 27-hydroxycholesterol were found in pl aques, while the concentration in non-atherosclerotic human vessels wa s lower by two orders of magnitude. The rabbit, which is particularly sensitive to dietary cholesterol and easily develops fatty streaks, ha d low plasma levels of 27-hydroxycholesterol, 3 ng/ml compared to 159 ng/ml in humans. The concentration of 27-hydroxycholesterol in the ath erosclerotic rabbit vessels was also lower compared to human atheroscl erotic plaques. The results are consistent with our hypothesis that st erol 27-hydroxylase may be utilized by human macrophages as a defence towards a high cholesterol load. This mechanism may be less important in some other species.