title: Modulation of gene expression by high and low density lipoproteins in human vascular smooth muscle cells.
abstract: Low density lipoprotein and its oxidized form has been implicated in the process of arteriosclerosis which involves growth-related events in the smooth muscle cells of the arterial wall. The induction of so-called early-growth response genes e.g. c-myc and c-fos can serve as an indicator for these growth-related events. In cultured human vascular smooth muscle cells, both LDL and HDL3 were individually capable of stimulating c-myc and c-fos expression in a concentration dependent manner. However, when they were used in combination, depending on the proportion of HDL3 to LDL, c-fos but not c-myc expression was less pronounced than with the single components. In contrast to HDL3 and LDL alone, a combination of the two lipoproteins also blunted both the expression of autoinduced transforming growth factor beta transcripts and the transforming growth factor beta-induced increase of c-fos mRNA. It is concluded that a) the inhibition of transforming growth factor beta autostimulation by HDL3 plus LDL may involve reduced AP-1 activity via a reduction of c-fos expression by the lipoprotein combination and b) the ratio HDL3:LDL might influence the pathogenesis of arteriosclerosis via growth-related events in the arterial wall.
authors.affiliation: Department of Research, Basel University Hospital, Switzerland.
authors.forename: A W
authors.initials: AW
authors.lastname: Hahn
authors.forename: F
authors.initials: F
authors.lastname: Ferracin
authors.forename: F R
authors.initials: FR
authors.lastname: Bühler
authors.forename: A
authors.initials: A
authors.lastname: Pletscher
mesh_terms: D001158:Arteries / Q000187:drug effects / Q000502:physiology; D015152:Blotting, Northern; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D005805:Genes, MHC Class I / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D011505:Protein-Tyrosine Kinases