School of Medicine, Fu-Jen Catholic University, Hsinchuang, Taipei 24205, Taiwan.
J Nutr Biochem. 2012 Jun;23(6):667-78. doi: 10.1016/j.jnutbio.2011.03.011. Epub 2011 Jul 30.
Previous studies have shown that an increased intake of dietary flavonoids is associated with a decreased risk of cardiovascular diseases (CVDs). PDGF is a major mitogen for vascular smooth muscle cell (VSMC) and participates in the pathogenesis of many CVDs. The study investigated whether the flavone chrysin affected PDGF functions in VSMCs and neointma formation in rat artery. We found that chrysin concentration-dependently inhibited PDGF-induced proliferation and chemotaxis and reduced PDGF signaling in VSMCs. Chrysin attenuated H(2)O(2) signaling and PDGF-induced reactive oxygen species production and NADPH oxidase activation but did not interfere with PDGF binding to VSMCs. The further analyses revealed that chrysin relieved PDGF-induced inhibition on activity of protein tyrosine phosphatase (PTP) and reduced PDGF-induced oxidation of PTP cysteinyl active site. Moreover, it inhibited PDGF receptor autophosphorylation induced by low-dose vanadate (an inhibitor for PTP). The effect of chrysin, but not of the flavonoid (-)-epigallocatechin-3-gallate and antioxidant N-acetylcysteine, on PDGF signaling and PTP activity was reversed by depletion of intracellular glutathione (GSH), suggesting an involvement of chrysin on GSH/glutaredoxin system for PTP reactivation. Finally, to demonstrate the effectiveness of chrysin in vivo, we showed that oral administration of chrysin before and after angioplasty could reduce neointima formation in balloon-injured carotid artery in rats. In conclusion, we provide here evidence that chrysin can regulate intracellular PTP activity during PDGF signaling, inhibits PDGF-induced VSMC proliferation and chemotaxis, and reduces arterial intima hyperplasia in vivo.
先前的研究表明，增加膳食类黄酮的摄入量与降低心血管疾病（CVDs）的风险有关。血小板衍生生长因子（PDGF）是血管平滑肌细胞（VSMC）的主要有丝分裂原，参与多种 CVDs 的发病机制。本研究旨在探讨黄酮 chrysin 是否影响 VSMCs 中的 PDGF 功能以及大鼠动脉中的新内膜形成。我们发现，chrysin 浓度依赖性地抑制 PDGF 诱导的增殖和趋化作用，并降低 VSMCs 中的 PDGF 信号。chrysin 减弱 H₂O₂信号和 PDGF 诱导的活性氧产生和 NADPH 氧化酶激活，但不干扰 PDGF 与 VSMCs 的结合。进一步的分析表明，chrysin 缓解了 PDGF 诱导的蛋白酪氨酸磷酸酶（PTP）活性抑制，并降低了 PDGF 诱导的 PTP 半胱氨酸活性位点氧化。此外，它抑制了低剂量钒酸盐（PTP 抑制剂）诱导的 PDGF 受体自身磷酸化。chrysin（而非黄酮（-）-表没食子儿茶素-3-没食子酸酯和抗氧化剂 N-乙酰半胱氨酸）对 PDGF 信号和 PTP 活性的作用可被细胞内谷胱甘肽（GSH）耗竭逆转，表明 chrysin 参与了 GSH/谷氧还蛋白系统对 PTP 再激活的作用。最后，为了证明 chrysin 在体内的有效性，我们表明血管成形术前和术后口服 chrysin 可减少大鼠球囊损伤颈动脉中的新生内膜形成。总之，我们在这里提供了证据表明，chrysin 可以在 PDGF 信号转导过程中调节细胞内 PTP 活性，抑制 PDGF 诱导的 VSMC 增殖和趋化作用，并减少体内动脉内膜增生。
