ABSTRACT
Objective To investigate the effect of lovaslatin on proliferation of cultured rat mesangial cells. Methods Cultured rat mesangial cells were stimulated by 10% fetal calf serum (FCS) or platelet-derived growth factor (PDGF) in the absence or the presence of lovastain and mevalonate metabolites. 5-Bromo-2-deoxyuridine incorporation was used to assess DNA synthesis. Results FCS or PDGF caused a marked stimulation of DNA synthesis in the mesangial cells. Lovastatin inhibited FCS or PDGF-stimulated BrdU incorporation and cell proliferation. Mevalonic acid, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented inhibitory effect of lovastatin on mesangial proliferation induced by FCS. Mevalonic acid and geranylgeranyl pyrophosphate also significantly reversed inhibitory effect of lovastatin on mesangial proliferation induced by PDGF. But farnesyl pyrophosphate only partly reversed inhibitory effect of lovastatin. Conclusions Lovastatin, by inhibiting the synthesis of isoprenoid metabolites of mevalonate, can suppress mesangial cell proliferation. It is possible to provide a new approach for treatment of proliferative glomerular diseases.