Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice.
Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice.
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miR-223 的造血缺陷可减轻小鼠光化学损伤引起的血栓形成。
DOI：
10.1038/s41598-017-01887-x
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发表时间：
2017
影响因子：
4.6
通讯作者：
Eitzman,DanielT
中科院分区：
文献类型：
--
作者：
Wang,Hui;Wang,Qian;Kleiman,Kyle;Guo,Chiao;Eitzman,DanielT
一些研究表明，血小板功能抑制后，血浆中源自血小板的MicroRNA（miR）-223水平降低，而另一些研究表明低血浆miR-223与高治疗血小板反应性之间存在相关性。本研究旨在探讨miR-223在动脉血栓形成中的作用。将光化学诱导的颈动脉血栓形成模型应用于miR-223缺陷型小鼠和同窝（WT）对照。与WT小鼠相比，miR-223缺陷小鼠表现出闭塞性血栓形成的时间显著延长，表明miR-223缺陷的保护作用。骨髓移植实验证实，miR-223的造血池是血栓形成时间差异的原因。输注WT血小板或源自WT血小板的细胞外囊泡均足以缩短miR-223缺陷型受体中的血栓形成时间。探讨血小板输注对IGF-1 R的影响。这些实验表明，血小板miR-223下调血管IGF-1 R。此外，抑制IGF-1 R消除了miR-223缺陷对血栓形成的保护作用。总之，血小板miR-223通过影响血管壁IGF-1 R，是内皮损伤后动脉血栓形成的调节因子。这项研究表明，血小板miR-223是预防动脉血栓形成的潜在治疗靶点。
Some studies have shown that levels of MicroRNA (miR)-223 derived from platelets in the plasma are reduced following inhibition of platelet function, while others have shown a correlation between low plasma miR-223 and high on-treatment platelet reactivity. The present study seeks to investigate the role of miR-223 in arterial thrombosis. A model of photochemical-induced carotid thrombosis was applied to miR-223 deficient mice and littermate (WT) controls. Mice deficient in miR-223 exhibited significantly prolonged times to occlusive thrombosis compared to WT mice indicating a protective effect of miR-223 deficiency. Bone marrow transplantation experiments confirmed that the hematopoietic pool of miR-223 was responsible for differences in thrombosis times. Transfusion of either WT platelets or extracellular vesicles derived from WT platelets were both sufficient to shorten thrombosis times in miR-223 deficient recipients. The effect of platelet transfusions on IGF-1R was explored. These experiments revealed that vascular IGF-1R was down-regulated by platelet miR-223. Furthermore, inhibition of IGF-1R abolished the protection conferred by miR-223 deficiency on thrombosis. In conclusion, platelet miR-223 is a regulator of arterial thrombosis following endothelial injury through effects on vascular wall IGF-1R. This study indicates that platelet miR-223 is a potential therapeutic target for prevention of arterial thrombosis.