Regulation of bone morphogenetic protein-2 expression in endothelial cells - Role of nuclear factor-kappa B activation by tumor necrosis factor-alpha, H2O2, and high intravascular pressure

Article

关键词: STIMULATES SUPEROXIDE PRODUCTION;    BMP-2 GENE-EXPRESSION;    OXIDATIVE STRESS;    NAD(P)H OXIDASE;    PULMONARY-HYPERTENSION;    CORONARY-ARTERIES;    SMOOTH-MUSCLE;    HYPERHOMOCYSTEINEMIA;    PATHOPHYSIOLOGY;    CHONDROCYTES;   

DOI  :  10.1161/01.CIR.0000164201.40634.1D

来源: SCIE

【 摘 要 】

Background-Recent studies suggest that bone morphogenetic protein-2 (BMP-2), a transforming growth factor-beta superfamily member cytokine, plays an important role both in vascular development and pathophysiological processes, including endothelial activation that is likely to contribute to the development of coronary atherosclerosis, yet the factors that regulate arterial expression of BMP-2 are completely unknown. We tested the hypothesis that BMP-2 expression in endothelial cells is governed by an H2O2 and nuclear factor (NF)-kappa B-dependent pathway that can be activated by both proinflammatory and mechanical stimuli. Methods and Results-The proinflammatory cytokine tumor necrosis factor (TNF)-alpha induced NF-kappa B activation and elicited significant increases in BMP-2 mRNA and protein in primary coronary arterial endothelial cells and human umbilical vein endothelial cells that were prevented by NF-kappa B inhibitors (pyrrolidine dithiocarbamate and SN-50), silencing of p65 (siRNA), or catalase. Administration of H2O2 also elicited NF-kappa B activation and BMP-2 induction. In organ culture, exposure of rat arteries to high pressure (160 mm Hg) elicited H2O2 production, nuclear translocation of NF-kappa B, and upregulation of BMP-2 expression. Although high pressure upregulated TNF-alpha, it appears that it directly regulates BMP-2 expression, because upregulation of BMP-2 was also observed in vessels of TNF-alpha knockout mice. Conclusions-Vascular BMP- 2 expression can be regulated by H2O2-mediated activation of NF-kappa B both by inflammatory stimuli and by high intravascular pressure.

【 授权许可】

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