Afrin S, Islam S, Patzkowsky K, et al. - Given their previous study establishing anti-leiomyoma effects of simvastatin, an anti-hyperlipidemic drug, through cellular, animal model and epidemiologic studies, researchers conducted a laboratory-based experimental study investigating if simvastatin influences altered mechanotransduction in leiomyoma cells. From five patients who underwent hysterectomy at the Department of Gynecology and Obstetrics at the Johns Hopkins Hospital, isolation of primary leiomyoma cells was done. For 48 h, treatment with simvastatin at increasing concentrations (0.001, 0.01, 0.1, 1μM or control) was provided to primary and immortalized human leiomyoma (HuLM) cells. Analysis revealed significant decrease in the protein expression of β1 integrin by 44% and type I collagen by 60% following simvastatin treatment of leiomyoma cells vs untreated leiomyoma cells. Simvastatin-treated cells decreased phosphorylation of FAK down to 26%-60% of control whereas it raised total FAK protein expression. A RhoA pull-down activation assay led to identification of reduced levels of active RhoA by 45%-85% in simvastatin-treated cells vs control. Consistent with impaired RhoA activation, simvastatin treatment led to a decrease in tumor gel contraction where gel area was 122%-153% larger compared with control. Furthermore, simvastatin treatment resulted in decreased levels of mechanical signaling proteins involved in β1 integrin downstream signaling, including AKAP13, ROCK1, MLCK, and cyclin D1. Results thereby support the value of simvastatin as a possible therapeutic tool to restore the altered state of mechanotransduction signaling in leiomyoma. .