Effects of HDL Subclasses on 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Human Fibroblasts

Monolayer cultures of normal human fibroblasts were used to study the effects of the main subclasses of high-density lipoproteins, HDL₂ and HDL₃, on 3-hydroxy-3-methylglutaryl CoA reductase (EC 1.1.1.34) activity. In this system, HDL₃ (d=1.1251.210 g/cm³) specifically induced HMG-CoA reductase activity. Evaluation of culture dynamics revealed that enzyme induction was restricted to the stationary phase of growth. When the cells were incubated with HDL₂ (d = 1.063-1.125 g/cm³), suppression of reductase activity was observed. Mixtures of HDL₂ and HDL₃ suppressed reductase activity when HDL₂ was greater than 35% of the total HDL. The suppressive effects of HDL₂, were abolished by treatment with cyclohexanedione and restored by regeneration of the arginyl residues, suggesting an apoprotein-mediated suppressive mechanism. These observations show that the cellular effects of HDL depend upon the stage of cell growth and the ratio of HDL subclasses in HDL as usually isolated.