Impaired Mitophagy: A New Potential Mechanism of Human Chronic Atrial Fibrillation.
Impaired Mitophagy: A New Potential Mechanism of Human Chronic Atrial Fibrillation.
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线粒体自噬受损：人类慢性心房颤动的新潜在机制
DOI：
10.1155/2020/6757350
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发表时间：
2020
影响因子：
2.1
通讯作者：
Jiang Z
中科院分区：
文献类型：
--
作者：
Zhou S;Dai W;Zhong G;Jiang Z
线粒体自噬是一种自噬反应，在细胞的生存、发育和稳态中起重要作用。据报道，线粒体吞噬功能障碍与多种心血管疾病有关。然而，线粒体自噬对心房颤动（AF）的影响仍然未知。因此，我们研究线粒体自噬在人类慢性AF中的确切作用。透射电镜观察线粒体形态结构。进行免疫荧光染色以分析线粒体与自噬体或溶酶体的共定位。选择43例心脏瓣膜病手术患者，其中慢性房颤患者21例，与窦性心律组比较，发现房颤患者心房肌细胞线粒体的大小和数量明显增加。此外，AF组中LC 3B II的表达和LC 3B II/LC 3B I的比率显著降低。AF组p62蛋白表达较SR组明显增高。免疫荧光染色和western blot结果显示AF组考克斯IV表达增强。双重免疫荧光染色显示，房颤患者心房肌细胞线粒体自噬缺陷是由于线粒体向自噬体输送过程中的功能障碍所致。首次发现线粒体吞噬功能受损与人类慢性房颤有关，线粒体自噬可能成为房颤潜在的治疗靶点。
Mitophagy is an autophagic response and plays essential roles in survival, development, and homeostasis of cells. It has been reported that mitophagic dysfunction is involved in several cardiovascular diseases. However, the effect of mitophagy on atrial fibrillation (AF) is still unknown. Therefore, we investigated the exact role of mitophagy in human chronic AF. Western blot was used to detect the protein abundance. The mitochondrial morphology and structure were observed by transmission electron microscopy. Immunofluorescent stainings were performed to analyze colocalization of mitochondria with autophagosomes or lysosomes. Totally, 43 patients with valvular heart disease undergoing cardiac surgery were selected, including 21 patients with chronic AF. Comparing with the sinus rhythm (SR) group, we found the size and number of mitochondria in atrial myocytes of patients with AF increased significantly. In addition, expression of LC3B II and LC3B II/LC3B I ratio was significantly decreased in the AF group. Moreover, the expression of p62 was markedly elevated in the AF group compared with that in the SR group. The results of immunofluorescence staining and western blot showed an enhanced expression of Cox IV in the AF group. Dual immunofluorescent stainings revealed that mitophagy defect in atrial myocytes of patients with AF resulted from dysfunction in the process of delivery of mitochondria into autophagosomes. For the first time, impaired mitophagy, during the phagocytosis of mitochondria, is associated with human chronic AF. Mitophagy could be a potential therapeutic target for AF.
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影响因子：
7.8
作者：
Marin-Aguilar, Fabiola;Lechuga-Vieco, Ana V.;Cordero, Mario D.
通讯作者：
Cordero, Mario D.
影响因子：
64.5
作者：
Erickson, Jeffrey R.;Joiner, Mei-ling A.;Anderson, Mark E.
通讯作者：
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影响因子：
24
作者：
Montaigne, David;Marechal, Xavier;Neviere, Remi
通讯作者：
Neviere, Remi
影响因子：
20.1
作者：
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通讯作者：
Gustafsson ÅB
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影响因子：
5.4
作者：
Yang Y;Zhao J;Qiu J;Li J;Liang X;Zhang Z;Zhang X;Fu H;Korantzopoulos P;Letsas KP;Tse G;Li G;Liu T
通讯作者：
Liu T