Placenta growth factor expression is regulated by hydrogen peroxide in vascular smooth muscle cells.
Placenta growth factor expression is regulated by hydrogen peroxide in vascular smooth muscle cells.
复制标题
DOI：
10.1152/ajpcell.00374.2010
复制
发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Jennifer H. Shaw;Lingjin Xiang;Anu Shah;W. Yin;P. Lloyd
中科院分区：
文献类型：
--
作者：
Jennifer H. Shaw;Lingjin Xiang;Anu Shah;W. Yin;P. Lloyd
当供血动脉闭塞时，血液通过预先存在的侧支血管转移。由血流增加引起的剪切应力提供了侧支循环扩张的初始生理刺激，该过程称为动脉生成。内皮细胞（EC）通过释放多种介质对增加的剪切力作出反应，这些介质可以作用于下面的平滑肌细胞（SMC）。已知胎盘生长因子（PLGF）介导动脉生成的某些方面，例如单核细胞向血管壁的募集。因此，我们测试了SMC PLGF表达是否受到EC释放的介质的影响。我们采用经EOMA EC处理4天的A10 SMC培养液作为模型。我们发现EC条件培养基能够上调A10 SMC中PLGF基因的表达。进一步的实验确定过氧化氢（H（2）O（2））是这种反应的关键介质。我们通过证明外源性H2O2特异性上调PLGF基因和蛋白表达，证实了这种机制在原代人冠状动脉SMC中的生理相关性。我们还证明了剪切应力的生理刺激将培养基中的内源性H（2）O（2）水平提高到发现增加PLGF表达的范围内。在本研究中，我们证明EC释放的H2O2对血管SMC中PLGF基因和蛋白表达起正性调节作用。据我们所知，这是第一个研究描述H（2）O（2）作为PLGF表达的调节剂，因此是PLGF驱动的动脉生成的上游介质。
When supply arteries become occluded, blood is diverted through preexisting collateral vessels. Shear stress arising from this increase in blood flow provides the initial physiological stimulus for expansion of the collateral circulation, a process termed arteriogenesis. Endothelial cells (EC) respond to increased shear stress by releasing a variety of mediators that can act on underlying smooth muscle cells (SMC). Placenta growth factor (PLGF) is known to mediate certain aspects of arteriogenesis, such as recruitment of monocytes to the vessel wall. Therefore, we tested whether SMC PLGF expression is influenced by mediators released by EC. We used A10 SMC cultured with medium that had been conditioned by EOMA EC for 4 days as a model. We found that EC-conditioned medium is able to upregulate PLGF gene expression in A10 SMC. Further experiments identified hydrogen peroxide (H(2)O(2)) as a key mediator of this response. We confirmed the physiological relevance of this mechanism in primary human coronary artery SMCs by demonstrating that exogenous H(2)O(2) specifically upregulates PLGF gene and protein expression. We also demonstrated that the physiological stimulus of shear stress raises endogenous H(2)O(2) levels in media into the range found to increase PLGF expression. In this study, we demonstrate that EC-released H(2)O(2) acts as a positive regulator of PLGF gene and protein expression in vascular SMC. To our knowledge, this is the first study to describe H(2)O(2) as a regulator of PLGF expression and therefore an upstream mediator of PLGF-driven arteriogenesis.