Cyclic fluctuations of 3-hydroxy-3-methylglutaryl-CoA reductase in aortic smooth muscle cell cultures

The cyclic fluctuations of HMG-CoA reductase activity and mRNA are reportedly related to feeding the cells in culture or to variations in food consumption by the animals over a 24-h cycle. In this work, we demonstrate cyclic increments in HMG-CoA reductase activity in smooth muscle cells (SMC) not associated with the culture feeding. Since reductase activity also shows a marked rise preceding the S phase, one of the major goals of the present work was to evaluate this dual role of reductase activity and mRNA fluctuations related to the cell cycle and to food intake in the SMC-C/SMC-Ch cultures derived from control-fed (SMC-C) and cholesterol-fed (SMC-Ch) chicks. The period and amplitude oscillations in HMG-CoA reductase activity varied depending on culture conditions: lipoprotein-deficient serum vs. FBS, young vs. senescent cells, or confluent vs. nonconfluent cultures. The HMG-CoA reductase mRNA concentration showed a marked rise after feeding not correlated to the fluctuation activity, suggesting posttranscriptional modulation. Reductase activity and mRNA were down-regulated in SMC-Ch. Since the nutritional culture conditions were the same in both cell lines, these findings indicate that consumption of a high-cholesterol diet by the animals prior to the establishment of the SMC cultures induced changes in the HMG-CoA reductase gene expression in-aortic SMC.