HMG-CoA reductase inhibitor lovastatin upregulates plasminogen activator production through RhoA-signaling in peritoneal cell line Met5A

This study was conducted to determine if hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor statin, known to protect postoperative adhesion in animal model, affect the expressing tissue-type plasminogen activator (tPA) in peritoneal cells in culture. Human peritoneal Met5A cells were used to examine the effects of hydrophobic statin lovastatin on the level of tPA. PA concentrations were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Active RhoA form was also examined. Lovastatin caused concentration-dependent tPA expression associated with fall of RhoA active level in Met5A cells. These lovastatin-induced changes were significantly overcome by the addition of geranylgeranyl pyrophosphate (intermediate of HMG-CoA pathway). A RhoA protein inhibitor C3 transferase mimicked the effects of lovastatin on the Met5A cells. These results suggest that lovastatin may be an effective stimulator of local peritoneal fibrinolytic activity, as it upregulates tPA expression in peritoneal Met5A cells through the reduction of RhoA geranylgeranylation. The extra-cholesterol lowering action of statin provides a new rationale to prevent peritoneal adhesion in postoperative patient.