The Journal of clinical investigation
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Products of intracellular mevalonate metabolism are essential for cell growth and proliferation. Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, blocks the formation of mevalonate and its metabolites, and has been shown to inhibit proliferation of several cell types. In vivo, lovastatin has reduced mesangial cellularity and glomerular injury in experimental renal disease. ⋯ By contrast, the isoprenoid farnesol (5 microM) largely prevented lovastatin inhibition of DNA synthesis. We conclude that mevalonate metabolism is essential for mesangial cell proliferation, possibly through the production of the isoprenoid farnesol. Moreover, the action of lovastatin to reduce experimental glomerular injury may involve a direct effect on mesangial cells.