title: 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.
  
  
  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.
authors.affiliation: Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha Hunan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Zhou
authors.forename: Xu-Ping
authors.initials: XP
authors.lastname: Li
authors.forename: Xiang-Qian
authors.initials: XQ
authors.lastname: Shen
authors.forename: Zhen-Fei
authors.initials: ZF
authors.lastname: Fang
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Liu
authors.forename: Shuang-Fa
authors.initials: SF
authors.lastname: Qiu
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Zhao
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D000069059:Atorvastatin; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000975:Antioxidants; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; D012333:RNA, Messenger; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; C099252:oxidized low density lipoprotein; C066229:prolinedithiocarbamate; D008315:Malondialdehyde; D011392:Proline; D000069059:Atorvastatin; D013482:Superoxide Dismutase