Mechanism of Accumulation of Cholesterol and Cholestanol in Tendons and the Role of Sterol 27-hydroxylase (CYP27A1)

• Sara von Bahr

  From the Divisions of Clinical Chemistry (S.v.B., U.D., I.B.), Orthopedics (T.M.), Pathology (N.P.), and Lung Medicine (P.R.), Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; and Department of Pharmacology and Toxicology (I.P.), University of Texas Medical Branch, Galvestone, Tex.

• Tomas Movin

  From the Divisions of Clinical Chemistry (S.v.B., U.D., I.B.), Orthopedics (T.M.), Pathology (N.P.), and Lung Medicine (P.R.), Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; and Department of Pharmacology and Toxicology (I.P.), University of Texas Medical Branch, Galvestone, Tex.

• Nikos Papadogiannakis

  From the Divisions of Clinical Chemistry (S.v.B., U.D., I.B.), Orthopedics (T.M.), Pathology (N.P.), and Lung Medicine (P.R.), Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; and Department of Pharmacology and Toxicology (I.P.), University of Texas Medical Branch, Galvestone, Tex.

• Irina Pikuleva

  From the Divisions of Clinical Chemistry (S.v.B., U.D., I.B.), Orthopedics (T.M.), Pathology (N.P.), and Lung Medicine (P.R.), Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; and Department of Pharmacology and Toxicology (I.P.), University of Texas Medical Branch, Galvestone, Tex.

• Per Rönnow

  From the Divisions of Clinical Chemistry (S.v.B., U.D., I.B.), Orthopedics (T.M.), Pathology (N.P.), and Lung Medicine (P.R.), Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; and Department of Pharmacology and Toxicology (I.P.), University of Texas Medical Branch, Galvestone, Tex.

• Ulf Diczfalusy

  From the Divisions of Clinical Chemistry (S.v.B., U.D., I.B.), Orthopedics (T.M.), Pathology (N.P.), and Lung Medicine (P.R.), Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; and Department of Pharmacology and Toxicology (I.P.), University of Texas Medical Branch, Galvestone, Tex.

• Ingemar Björkhem

  From the Divisions of Clinical Chemistry (S.v.B., U.D., I.B.), Orthopedics (T.M.), Pathology (N.P.), and Lung Medicine (P.R.), Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; and Department of Pharmacology and Toxicology (I.P.), University of Texas Medical Branch, Galvestone, Tex.

抄録

Objective — Tendon xanthomas are deposits of lipids and connective tissue commonly found in hypercholesterolemic patients. Macrophages are likely to be responsible for the lipid accumulation. Normolipidemic patients with the rare disease cerebrotendinous xanthomatosis, lacking the enzyme sterol 27-hydroxylase (CYP27A1), develop prominent xanthomas in tendons and brain containing both cholestanol and cholesterol, with a cholestanol:cholesterol ratio higher than that in the circulation. Because of its ability to convert cholesterol into polar metabolites that leave the cells faster, CYP27A1 has been suggested to be an antiatherogenic enzyme. The hypothesis was tested that tendons contain CYP27A1 that may be of importance for the normal efflux of both steroids. Methods and Results — Western blotting and combined gas chromatography-mass spectrometry showed that human tendons contain significant amounts of CYP27A1 and its product, 27-hydroxycholesterol. Immunohistochemistry showed that CYP27A1 is present in macrophages and tenocytes. The tendons also contained cholestanol, with a cholestanol:cholesterol ratio slightly higher than that in the circulation. Recombinant human CYP27A1, and cultured human macrophages containing this enzyme, had similar activity toward cholesterol and cholestanol. After loading of macrophages with labeled cholesterol and cholestanol, there was an efflux of these steroids in both unmetabolized and 27-oxygenated form, resulting in a significant cellular accumulation of cholestanol compared with cholesterol. Conclusion — The results are consistent with the possibility that CYP27A1 is of importance for the efflux of both cholesterol and cholestanol from tendons.

収録刊行物

• Arteriosclerosis, Thrombosis, and Vascular Biology

  Arteriosclerosis, Thrombosis, and Vascular Biology 22 (7), 1129-1135, 2002-07

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Cardiology and Cardiovascular Medicine

詳細情報

• CRID: 1362544419252122752
• NII論文ID: 30023094016
• NII書誌ID: AA11029972
• DOI: 10.1161/01.atv.0000022600.61391.a5
• ISSN: 15244636
• ISSN: 10795642
• ISSN: http://id.crossref.org/issn/10795642
• Web Site: https://www.ahajournals.org/doi/full/10.1161/01.ATV.0000022600.61391.A5
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