Expression of cholesterol 27-hydroxylase in peripheral blood monocytes/macrophages: An independent risk factor for coronary artery disease?

Reiss A. Galloway, E. Grossi, D. Schwartz, S. Lyer, F. Pasternack, N. Javitt

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Abstract

Cholesterol 27-hydroxylase expression in aortic endothelium (J. Lipid Res. 1994; 35:1026-30) implies a role for this enzyme and its cholesterol metabolite, 27-hydroxycholesterol, in die atherogenic process. Evidence supporting a role in atherogenesis includes the downregulation of cholesterol synthesis and low density lipoprotein receptor activity by 27-hydroxycholesterol and the occurence of accelerated atherosclerosis in individuals with genetically determined 27-hydroxylase deficiency. To further evaluate die role of cholesterol 27-hydroxylase in atheroma formation, we designed unique oligonudeotide primers for the detection of 27-hydroxylase mRNA by reverse transcription-polymerase chain reaction (RT-PCR). The primers span a 311 basepair segment encompassing nucleotides 491-802 of the 27-hydroxylase cDNA. The amplified fragment crosses the junction of die third and fourth exons and has been confirmed to be 100% homologous to the published sequence. The RT-PCR assay was applied to mRNA derived from monocytes isolated from the peripheral blood of 5 healthy volunteers. In all cases, die amplification product was detected by edudium bromide staining after agarose gel electrophoresis. Cultured macrophages transformed from peripheral blood monocytes of 5 healthy subjects also expressed 27-hydroxylase by RT-PCR. Although the atherogenic process is complex, it is well-established that foam cell formation, endothelial cell injury and neointimal proliferation are intrinsic to lesion formation. Local production of 27-hydroxycholesterol by cells participating in atherogenesis may serve to limit the extent of atheroma formation. In addition to the genetically determined disease, loss of this local activity may also be acquired and could account for accelerated atherosclerosis in patients with normal lipoprotein profiles.

Original languageEnglish
Pages (from-to)282a
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - 1996
Externally publishedYes

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