Exercise promotes angiogenesis by enhancing endothelial cell fatty acid utilization via liver-derived extracellular vesicle miR-122-5p.
Exercise promotes angiogenesis by enhancing endothelial cell fatty acid utilization via liver-derived extracellular vesicle miR-122-5p.
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运动通过肝源性细胞外囊泡 miR-122-5p 增强内皮细胞脂肪酸利用，从而促进血管生成
DOI：
10.1016/j.jshs.2021.09.009
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发表时间：
2022-07
影响因子：
11.7
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Lou, Jing;Wu, Jie;Feng, Mengya;Dang, Xue;Wu, Guiling;Yang, Hongyan;Wang, Yan;Li, Jia;Zhao, Yong;Shi, Changhong;Liu, Jiankang;Zhao, Lin;Zhang, Xing;Gao, Feng
运动通过上调循环miR-122- 5 p促进血管生成和组织修复。运动引起的miR-122- 5 p上调主要来源于肝脏，并通过细胞外囊泡穿梭。miR-122- 5 p通过靶向内皮细胞中的AGPAT 1增强脂肪酸的使用来促进血管生成。血管生成构成了运动诱导的有益作用的主要机制。我们的前期研究发现了一组运动后差异表达的细胞外囊泡microRNA（miRNAs），并发现其中一些作为运动因子。然而，这些细胞外囊泡miRNAs是否介导运动诱导的血管生成仍不清楚。在C57 BL/6小鼠中使用9天的跑台训练作为运动模型。肝脏特异性腺相关病毒8用于敲低microRNA-122- 5 p（miR-122- 5 p）。体外培养人脐静脉内皮细胞。在这些差异表达的细胞外囊泡miRNA中，miR-122- 5 p被鉴定为有效的促血管生成因子，其激活血管内皮生长因子信号传导并促进体内和体外血管生成。运动增加了miR-122- 5 p的循环水平，miR-122- 5 p主要由肝脏产生，并通过小鼠的细胞外囊泡穿梭。循环miR-122- 5 p的抑制或miR-122- 5 p的肝脏特异性敲低显著消除了骨骼肌中运动诱导的促血管生成作用，并且运动改善了小鼠的肌肉性能。从机制上讲，miR-122- 5 p通过改变内皮细胞对脂肪酸的底物偏好来促进血管生成，并且miR-122- 5 p通过靶向1-酰基-sn-甘油-3-磷酸酰基转移酶（AGPAT 1）来上调内皮细胞脂肪酸利用。此外，miR-122- 5 p增加了小鼠皮损周围皮肤组织中的毛细血管密度并加速了伤口愈合。这些发现表明，运动通过上调肝脏来源的细胞外囊泡miR-122- 5 p促进血管生成，这通过靶向内皮细胞中的AGPAT 1增强脂肪酸利用，突出了miR-122- 5 p在组织修复中的治疗潜力。
Exercise promotes angiogenesis and tissue repair through upregulation of circulating miR-122-5p. The upregulated miR-122-5p brought about by exercise is derived mainly from the liver and is shuttled by extracellular vesicles. miR-122-5p promotes angiogenesis through the enhancement of fatty acid use by targeting AGPAT1 in endothelial cells. Angiogenesis constitutes a major mechanism responsible for exercise-induced beneficial effects. Our previous study identified a cluster of differentially expressed extracellular vesicle microRNAs (miRNAs) after exercise and found that some of them act as exerkines. However, whether these extracellular vesicle miRNAs mediate the exercise-induced angiogenesis remains unknown. A 9-day treadmill training was used as an exercise model in C57BL/6 mice. Liver-specific adeno-associated virus 8 was used to knock down microRNA-122-5p (miR-122-5p). Human umbilical vein endothelial cells were used in vitro. Among these differentially expressed extracellular vesicle miRNAs, miR-122-5p was identified as a potent pro-angiogenic factor that activated vascular endothelial growth factor signaling and promoted angiogenesis both in vivo and in vitro. Exercise increased circulating levels of miR-122-5p, which was produced mainly by the liver and shuttled by extracellular vesicles in mice. Inhibition of circulating miR-122-5p or liver-specific knockdown of miR-122-5p significantly abolished the exercise-induced pro-angiogenic effect in skeletal muscles, and exercise-improved muscle performance in mice. Mechanistically, miR-122-5p promoted angiogenesis through shifting substrate preference to fatty acids in endothelial cells, and miR-122-5p upregulated endothelial cell fatty-acid utilization by targeting 1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT1). In addition, miR-122-5p increased capillary density in perilesional skin tissues and accelerated wound healing in mice. These findings demonstrated that exercise promotes angiogenesis through upregulation of liver-derived extracellular vesicle miR-122-5p, which enhances fatty acid utilization by targeting AGPAT1 in endothelial cells, highlighting the therapeutic potential of miR-122-5p in tissue repair.
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影响因子：
64.5
作者：
De Bock, Katrien;Georgiadou, Maria;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
DOI：
10.1126/science.aaw2622
发表时间：
2020-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Horowitz AM;Fan X;Bieri G;Smith LK;Sanchez-Diaz CI;Schroer AB;Gontier G;Casaletto KB;Kramer JH;Williams KE;Villeda SA
通讯作者：
Villeda SA
影响因子：
15.9
作者：
Castoldi, Mirco;Spasic, Maja Vujic;Muckenthaler, Martina U.
通讯作者：
Muckenthaler, Martina U.
影响因子：
20.8
作者：
Diebold, Lauren P.;Gil, Hyea Jin;Chandel, Navdeep S.
通讯作者：
Chandel, Navdeep S.
DOI：
10.1007/978-1-4939-9133-4_18
发表时间：
2019-01-01
期刊：
EXTRACELLULAR MATRIX
影响因子：
--
作者：
Kastana, Pinelopi;Zahra, Fatema Tuz;Papadimitriou, Evangelia
通讯作者：
Papadimitriou, Evangelia