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Circ J ; 72(5): 807-12, 2008 May.
Article in English | MEDLINE | ID: mdl-18441463

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.


Subject(s)
Bone Morphogenetic Proteins/genetics , Endothelial Cells/drug effects , Heptanoic Acids/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Lipoproteins, LDL/pharmacology , Pyrroles/pharmacology , Transforming Growth Factor beta/genetics , Antioxidants/pharmacology , Atorvastatin , Bone Morphogenetic Protein 2 , Bone Morphogenetic Proteins/metabolism , Cell Nucleus/metabolism , Cells, Cultured , Cytoplasm/metabolism , Down-Regulation/drug effects , Drug Interactions , Endothelial Cells/cytology , Endothelial Cells/metabolism , Gene Expression/drug effects , Humans , Malondialdehyde/metabolism , Proline/analogs & derivatives , Proline/pharmacology , RNA, Messenger/metabolism , Superoxide Dismutase/metabolism , Thiocarbamates/pharmacology , Transcription Factor RelA/metabolism , Transforming Growth Factor beta/metabolism , Umbilical Veins/cytology
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