MODULATION OF GENE-EXPRESSION BY HIGH AND LOW-DENSITY LIPOPROTEINS IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS

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 β transcripts and the transforming growth factor β- induced increase of c-fos mRNA. It is concluded that a) the inhibition of transforming growth factor β 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. © 1991.