Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, Michigan, USA.
Department of Cardiology, the Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Sci Rep. 2017 May 9;7(1):1606. doi: 10.1038/s41598-017-01887-x.
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.
一些研究表明，在抑制血小板功能后，血浆中来自血小板的 MicroRNA (miR)-223 水平降低，而其他研究则表明低血浆 miR-223 与高治疗后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。应用光化学诱导的颈动脉血栓形成模型研究 miR-223 缺陷小鼠及其同窝对照（WT）。与 WT 小鼠相比，miR-223 缺陷小鼠的闭塞性血栓形成时间明显延长，表明 miR-223 缺陷具有保护作用。骨髓移植实验证实，miR-223 的造血池是导致血栓形成时间差异的原因。WT 血小板或 WT 血小板衍生的细胞外囊泡的输注均可缩短 miR-223 缺陷受者的血栓形成时间。还探索了血小板输注对 IGF-1R 的影响。这些实验表明，血小板 miR-223 通过对血管壁 IGF-1R 的作用来调节内皮损伤后的动脉血栓形成。综上所述，血小板 miR-223 是内皮损伤后动脉血栓形成的调节剂，通过对血管壁 IGF-1R 的作用。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。
