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首页> 外文期刊>Physiological Reports >Mitochondrial mitophagy in mesenteric artery remodeling in hyperhomocysteinemia
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Mitochondrial mitophagy in mesenteric artery remodeling in hyperhomocysteinemia

机译：高同型半胱氨酸血症在肠系膜动脉重塑中的线粒体线粒体吞噬

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AbstractAlthough high levels of homocysteine also termed as hyperhomocysteinemia (HHcy) has been associated with inflammatory bowel disease and mesenteric artery occlusion, the mitochondrial mechanisms behind endothelial dysfunction that lead to mesenteric artery remodeling are largely unknown. We hypothesize that in HHcy there is increased mitochondrial fission due to altered Mfn-2/Drp-1 ratio, which leads to endothelial dysfunction and collagen deposition in the mesenteric artery inducing vascular remodeling. To test this hypothesis, we used four groups of mice: (i) WT (C57BL/6J); (ii) mice with HHcy (CBS+/−); (iii) oxidative stress resistant mice (C3H) and (iv) mice with HHcy and oxidative stress resistance (CBS+/−/C3H). For mitochondrial dynamics, we studied the expression of Mfn-2 which is a mitochondrial fusion protein and Drp-1 which is a mitochondrial fission protein by western blots, real-time PCR and immunohistochemistry. We also examined oxidative stress markers, endothelial cell, and gap junction proteins that play an important role in endothelial dysfunction. Our data showed increase in oxidative stress, mitochondrial fission (Drp-1), and collagen deposition in CBS+/− compared to WT and C3H mice. We also observed significant down regulation of Mfn-2 (mitochondrial fusion marker), CD31, eNOS and connexin 40 (gap junction protein) in CBS+/− mice as compared to WT and C3H mice. In conclusion, our data suggested that HHcy increased mitochondrial fission (i.e., decreased Mfn-2/Drp-1 ratio, causing mitophagy) that leads to endothelial cell damage and collagen deposition in the mesenteric artery. This is a novel report on the role of mitochondrial dynamics alteration defining mesenteric artery remodeling.
机译：摘要尽管高水平的半胱氨酸也被称为高同型半胱氨酸血症（HHcy）与炎症性肠病和肠系膜动脉闭塞有关，但内皮功能障碍背后导致肠系膜动脉重塑的线粒体机制尚不清楚。我们假设在HHcy中，由于Mfn-2 / Drp-1比率的改变而增加了线粒体裂变，从而导致内皮功能障碍和肠系膜动脉中胶原沉积，从而引起血管重塑。为了验证这一假设，我们使用了四组小鼠：（i）WT（C57BL / 6J）; （ii）具有HHcy（CBS +/-）的小鼠; （iii）抗氧化应激的小鼠（C3H）和（iv）具有HHcy和抗氧化应激的小鼠（CBS + /-/ C3H）。对于线粒体动力学，我们通过蛋白质印迹，实时PCR和免疫组织化学研究了线粒体融合蛋白Mfn-2和线粒体裂变蛋白Drp-1的表达。我们还检查了氧化应激标记，内皮细胞和间隙连接蛋白在内皮功能障碍中起重要作用。我们的数据显示，与WT和C3H小鼠相比，CBS +/-中氧化应激，线粒体裂变（Drp-1）和胶原蛋白沉积增加。我们还观察到，与WT和C3H小鼠相比，CBS +/-小鼠中Mfn-2（线粒体融合标志物），CD31，eNOS和连接蛋白40（间隙连接蛋白）显着下调。总之，我们的数据表明HHcy增加了线粒体裂变（即Mfn-2 / Drp-1比率降低，引起线粒体吞噬），导致内皮细胞损伤和肠系膜动脉中的胶原沉积。这是有关线粒体动力学改变定义肠系膜动脉重塑作用的新报道。

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