Mevalonate pathway and isoprenoids regulate human bronchial myocyte proliferation

Abstract

The role of mevalonate and geranylgeraniol in the control of cellular proliferation of cultured human bronchial myocytes was examined by investigating the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in mevalonate synthesis. Simvastatin inhibited the rate of growth of human bronchial smooth muscle cells in a concentration-dependent manner, with an IC₅₀ value of 0.97±0.1 μM. Mevalonate (100 μM), as well as geranylgeraniol (5 μM), at their highest non-toxic concentrations, restored cell proliferation to control levels.