Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A potential role for sterol 27-hydroxylase in atherogenesis
Autore:
Shanahan, CM; Carpenter, KLH; Cary, NRB;
Indirizzi:
Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England Univ Cambridge Cambridge England CB2 2QQ Med, Cambridge CB2 2QQ, England Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England Univ Cambridge Cambridge England CB2 1QP hol, Cambridge CB2 1QP, England Papworth Hosp, Dept Pathol, Cambridge CB3 8RE, England Papworth Hosp Cambridge England CB3 8RE thol, Cambridge CB3 8RE, England
Titolo Testata:
ATHEROSCLEROSIS
fascicolo: 2, volume: 154, anno: 2001,
pagine: 269 - 276
SICI:
0021-9150(20010201)154:2<269:APRFS2>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN MONOCYTE-MACROPHAGES; ACID BIOSYNTHETIC ENZYME; SMOOTH-MUSCLE CELLS; CEREBROTENDINOUS XANTHOMATOSIS; MITOCHONDRIAL CYTOCHROME-P-450; ATHEROSCLEROTIC PLAQUES; LIPID CORE; CHOLESTEROL; LIVER; IDENTIFICATION;
Keywords:
atherosclerosis (human); lesions; normal artery; sterol 27-hydroxylase; macrophages; smooth muscle cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Shanahan, CM Univ Cambridge, Addenbrookes Hosp, Dept Med, Box 157,Hills Rd, Cambridge CB2 2QQ, England Univ Cambridge Box 157,Hills Rd Cambridge England CB2 2QQ nd
Citazione:
C.M. Shanahan et al., "A potential role for sterol 27-hydroxylase in atherogenesis", ATHEROSCLER, 154(2), 2001, pp. 269-276

Abstract

Objective: 27-hydroxycholesterol is the product of the mitochondrial cytochrome P450 sterol 27-hydroxylase, a key enzyme in cholesterol metabolism present in most tissues of the body. 27-hydroxycholesterol increases in abundance with progression of human atherosclerotic lesions, therefore the aim of this study was to determine the pattern of sterol 27-hydroxylase gene expression in normal and diseased arteries and to identify the cell types responsible for its expression, Methods: Reverse transcription-polymerase chainreaction (RT-PCR) analysis and in situ hybridisation, utilising a sterol 27-hydroxylase cDNA probe, and immunohistochemistry, utilising an antibody to sterol 27-hydroxylase, together with an antibody to smooth muscle cell alpha -actin and an antibody to CD68, a marker for macrophages, were used to study expression of 27-hydroxylase in arterial specimens. In addition, RT-PCR was used to study expression of 27-hydroxylase in cultured macrophages and smooth muscle cells. Results: Semi-quantitative RT-PCR analysis of normal and atherosclerotic human aortas showed that 27-hydroxylase is constitutively expressed in the normal artery wall, and is substantially up-regulatedin atherosclerosis. RT-PCR analysis of 27-hydroxylase expression in vitro demonstrated that macrophages constitutively express high levels throughouttheir differentiation in culture whilst de-differentiated vascular smooth muscle cells express very low levels. In situ hybridisation revealed that in normal artery and fatty streaks, expression of mRNA for 27-hydroxylase was low in the media, but higher in intimal smooth muscle cells. The macrophages of fatty streaks expressed low or undetectable levels of 27-hydroxylase. However in advanced lesions the highest expression of 27-hydroxylase was detectable in macrophages. Immunohistochemistry demonstrated that high levels of 27-hydroxylase protein occurred in macrophages near the shoulder region of plaques, at the edge of the lipid core. Conclusions: 27-hydroxylase may constitute a protective mechanism for removing cholesterol from macrophages and smooth muscle cells. Genetic heterogeneity resulting in differencesin sterol 27-hydroxylase activity between individuals may affect their ability to deal with accumulated cholesterol in the arterial intima, and hencetheir relative degree of predisposition to atherosclerosis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/02/20 alle ore 03:05:40