title: Expression and synthesis of TGFbeta1 is induced in macrophages by 9-oxononanoyl cholesterol, a major cholesteryl ester oxidation product.
abstract: Within the broad variety of compounds generated via oxidative reactions in low density lipoproteins (LDL) and subsequently found in the atherosclerotic plaque, are aldehydes still esterified to the parent lipid and termed core-aldehydes. The most represented cholesterol core-aldehyde in LDL is 9-oxononanoyl cholesterol (9-ONC), an oxidation product of cholesteryl linoleate. Here we report that 9-ONC, at concentration actually detectable in biological material, significantly up-regulates the expression and the synthesis of the pro-fibrogenic cytokine transforming growth factor beta1 (TGFbeta1) by cultured macrophages. As previously demonstrated for other lipid oxidation products present in LDL, namely a biologically representative mixture of oxysterols and the unesterified aldehyde 4-hydroxynonenal, these effects on TGFbeta1 by 9-ONC further points to LDL lipid oxidation as a powerful source of pro-fibrogenic stimuli.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, S. Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sottero
authors.forename: Paola
authors.initials: P
authors.lastname: Gamba
authors.forename: Monica
authors.initials: M
authors.lastname: Longhi
authors.forename: Fanny
authors.initials: F
authors.lastname: Robbesyn
authors.forename: Peter M
authors.initials: PM
authors.lastname: Abuja
authors.forename: Rudolf J
authors.initials: RJ
authors.lastname: Schaur
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Leonarduzzi
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
chemical_list: C114702:9-oxononanoyl cholesterol; D011506:Proteins; D012333:RNA, Messenger; D002784:Cholesterol