The effects of LDL cholesterol and pitavastatin treatment on fibroblast migration, SREBP-2, and LDLr expression

Abstract

Most non-healing wounds show a lack of cell migration contributing to chronic inflammation and infection. Cholesterol levels in the blood may have an impact on cell migration, as migrating cells demonstrate a need for cholesterol in order to synthesize additional cell membranes. Statins are a popular drug used for lowering blood cholesterol by competitive inhibition of HMG CoA reductase, a pivotal step in the cholesterol synthesis pathway. In this study, we examined the effects of low-density lipoprotein (LDL) and statin treatment on fibroblasts in vitro. A cholesterol ELISA was utilized to examine cholesterol levels in cultured fibroblasts following treatment with pitavastatin or LDL. A scratch-test assay was performed to examine fibroblast migration following treatment in addition to the MTT cell proliferation assay. Western blot analysis was used to examine the cholesterol signalling protein SREBP-2 and LDLr expression in treated cells. LDL treatment enhanced cell proliferation and migration, while both were inhibited by pitavastatin. Pitavastatin increased both SREBP-2 and LDLr expression in treated cells compared to LDL and vehicle control treatments. These results indicate pitavastatin inhibits cell migration and the cellular response is to increase cholesterol levels to make up for the inhibition of cholesterol synthesis though the mevalonate pathway. This could have significant effects on cell migration and wound healing in vivo for patients with inhibited wound healing responses on statin therapy.