The effect of simvastatin treatment on TNF-alpha-induced inflammation in human vascular endothelial cells (HUVECs)

Authors: BÜŞRA GÖRGÜN, BETÜL İŞİNER KAYA, KÜBRA KAYA, LEYLA DİDEM KOZACI

Abstract: This study investigates the effects of simvastatin (SMV) on human umbilical vein endothelial cells (HUVECs) inflamed by tumor necrosis factor-alpha (TNF-a). Cells were treated with simvastatin (5 μM, 10 μM, and 50 μM) with/without TNF (20 ng/mL). The effects of simvastatin on the proliferation of cells were examined, and its cytotoxic effect was determined by lactate dehydrogenase (LDH) assays. Metalloproteinase expression (MMP-2 and MMP-9) levels of SMV at different concentrations were determined by qPCR, and protein levels were determined by Western blot. The increasing concentrations of SMV down-regulated the expression levels of MMPs. After stimulation with TNF-a, the effect of SMV at different concentrations on wound healing time in case of wound formation was examined. The results interestingly indicated that SMV delayed the closure time 2.5-fold when it was administered alone to HUVECs but did not change the wound closure time in inflamed conditions. The study suggests that inflammation is a required condition in wound healing, and in the absence of inflammation, SMV treatment delays wound healing in vitro.

Keywords: Human umbilical vein endothelial cell, simvastatin, tumor necrosis factor-alpha, matrix metalloproteinase, wound healing

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