MEVALONATE PATHWAY AND ISOPRENOIDS REGULATE HUMAN BRONCHIAL MYOCYTE PROLIFERATION

The role of mevalonate and geranylgeraniol in the control of cellular proliferation of cultured human bronchial myocytes was examined by inv estigating the effect of simvastatin, an inhibitor of 3-hydroxy-3-meth ylglutaryl coenzyme A reductase, the rate-limiting enzyme in mevalonat e synthesis. Simvastatin inhibited the rate of growth of human bronchi al smooth muscle cells in a concentration-dependent manner, with an IC 50 value of 0.97 +/- 0.1 mu M. Mevalonate (100 mu M), as well as geran ylgeraniol (5 mu M), at their highest non-toxic concentrations, restor ed cell proliferation to control levels.