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 HDL 3 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 HDL 3 to LDL, c-fos but not c-myc expression was less pronounced than with the single components. In contrast to HDL 3 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 HDL 3 plus LDL may involve reduced AP-1 activity via a reduction of c-fos expression by the lipoprotein combination and b) the ratio HDL 3 :LDL might influence the pathogenesis of arteriosclerosis via growth- related events in the arterial wall.