Atorvastatin downregulates BMP-2 expression induced by oxidized low-density lipoprotein in human umbilical vein endothelial cells.

ABSTRACT

BACKGROUND: Bone morphogenetic protein-2 (BMP-2) plays a key role both in vascular development and pathophysiological processes. However, the effects of oxidized low-density lipoprotein (ox-LDL) combined with atorvastatin on BMP-2 expression are entirely unknown in human umbilical vein endothelial cells (HUVECs). The present study investigates the effects of ox-LDL on BMP-2 expression. Furthermore, the influence of atorvastatin on ox-LDL-induced BMP-2 expression is also examined. METHODS AND RESULTS: The HUVECs were treated by ox-LDL or combined with pyrrolidine dithiocarbamate (PDTC) or atorvastatin. The expression level of BMP-2 mRNA was examined by real-time PCR and RT-PCR analysis. The expression of BMP-2 protein was assayed by enzyme-linked immunosorbent assay. The malondialdehyde (MDA) and activities of total superoxide dismutase (SOD) were detected by routine methods. The activation of nuclear factor kappaB (NF-kappaB) in HUVECs was determined using an assay kit from active motif and western blot analysis. Ox-LDL treatment significantly increased BMP-2 expression, which is associated with NF-kappaB activation, but BMP-2 expression was suppressed by treatment with PDTC or atorvastatin. Furthermore, the increase in MDA levels and decrease in activities of total SOD caused by ox-LDL treatment were reversed by the treatment of PDTC or atorvastatin. CONCLUSIONS: Ox-LDL-induced BMP-2 expression was suppressed by PDTC or atorvastatin treatment. The effects of atorvastatin might contribute to the mechanisms by inhibiting NF-kappaB activation.