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Localization of sterol 27-hydroxylase immuno-reactivity in human atherosclerotic plaques.

Abstract
It has recently been shown that extrahepatic cells can eliminate intracellular cholesterol by enzymatic conversion into 27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholestenoic acid. Using immunohistochemical methods, we studied the presence of the enzyme responsible for these conversions, sterol 27-hydroxylase, in human carotid atherosclerotic plaques. All plaques examined were found to contain sterol 27-hydroxylase immuno-reactive cells. While some endothelial cells stained for sterol 27-hydroxylase, the majority of the immunoreactive cells co-localized with macrophages. Accumulation of sterol 27-hydroxylase-positive cells were often observed in macrophage-rich core regions of complicated lesions. High concentrations of 27-hydroxycholesterol were found in plaques, while the concentration in non-atherosclerotic human vessels was lower by two orders of magnitude. The rabbit, which is particularly sensitive to dietary cholesterol and easily develops fatty streaks, had low plasma levels of 27-hydroxycholesterol, 3 ng/ml compared to 150 ng/ml in humans. The concentration of 27-hydroxycholesterol in the atherosclerotic rabbit vessels was also lower compared to human atherosclerotic plaques. The results are consistent with our hypothesis that sterol 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.
AuthorsM Crisby, J Nilsson, V Kostulas, I Björkhem, U Diczfalusy
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1344 Issue 3 Pg. 278-85 (Feb 18 1997) ISSN: 0006-3002 [Print] Netherlands
PMID9059518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hydroxycholesterols
  • 27-hydroxycholesterol
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase
Topics
  • Animals
  • Arteriosclerosis (enzymology, metabolism)
  • Carotid Arteries (chemistry)
  • Cholestanetriol 26-Monooxygenase
  • Cytochrome P-450 Enzyme System (analysis)
  • Endothelium, Vascular (enzymology)
  • Humans
  • Hydroxycholesterols (analysis, blood)
  • Immunoenzyme Techniques
  • Macrophages (enzymology)
  • Male
  • Rabbits
  • Steroid Hydroxylases (analysis)
  • Veins (enzymology)

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