Mitochondrial transplantation attenuates hypoxic pulmonary hypertension.
Mitochondrial transplantation attenuates hypoxic pulmonary hypertension.
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线粒体移植减轻缺氧性肺动脉高压
DOI：
10.18632/oncotarget.10596
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发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Hu Q
中科院分区：
文献类型：
--
作者：
Zhu L;Zhang J;Zhou J;Lu Y;Huang S;Xiao R;Yu X;Zeng X;Liu B;Liu F;Sun M;Dai M;Hao Q;Li J;Wang T;Li T;Hu Q
线粒体在缺氧性肺血管收缩和肺血管重塑的发生中是必不可少的，这两个方面是导致肺动脉高压的两个主要方面，肺动脉高压是一种不治之症。然而，低氧可导致股动脉等全身动脉的松弛，线粒体的异质性控制着体外培养的肺和股动脉平滑肌细胞对低氧的不同反应。这项研究的目的是确定是否可以在体内实验地利用线粒体的异质性来作为一种潜在的治疗肺动脉高压的方法。将完整的线粒体通过静脉注射的方式移植到SD大鼠的肺动脉平滑肌细胞内。免疫荧光染色和超微结构检查证实了外源性线粒体在细胞内的分布，并揭示了线粒体可能部分通过细胞间隙和细胞间连接从肺动脉内皮细胞转移到平滑肌细胞。股动脉平滑肌细胞来源的线粒体移植可抑制急性低氧性肺血管收缩，减轻慢性低氧性肺血管重塑，从而预防或治愈慢性低氧大鼠的肺动脉高压。我们的发现表明，线粒体移植对于探索一种新的治疗和预防肺动脉高压的策略具有潜在的意义。
Mitochondria are essential for the onset of hypoxia-induced pulmonary vasoconstriction and pulmonary vascular-remodeling, two major aspects underlying the development of pulmonary hypertension, an incurable disease. However, hypoxia induces relaxation of systemic arteries such as femoral arteries and mitochondrial heterogeneity controls the distinct responses of pulmonary versus femoral artery smooth muscle cells to hypoxia in vitro. The aim of this study was to determine whether mitochondrial heterogeneity can be experimentally exploited in vivo for a potential treatment against pulmonary hypertension. The intact mitochondria were transplanted into Sprague-Dawley rat pulmonary artery smooth muscle cells in vivo via intravenous administration. The immune-florescent staining and ultrastructural examinations on pulmonary arteries confirmed the intracellular distribution of exogenous mitochondria and revealed the possible mitochondrial transfer from pulmonary artery endothelial cells into smooth muscle cells in part through their intercellular space and intercellular junctions. The transplantation of mitochondria derived from femoral artery smooth muscle cells inhibited acute hypoxia-triggered pulmonary vasoconstriction, attenuated chronic hypoxia-induced pulmonary vascular remodeling, and thus prevented the development of pulmonary hypertension or cured the established pulmonary hypertension in rats exposed to chronic hypoxia. Our findings suggest that mitochondrial transplantation possesses potential implications for exploring a novel therapeutic and preventive strategy against pulmonary hypertension.