Peters Linsey J F, Baaten Constance C F M J, Maas Sanne L, Lu Chang, Nagy Magdolna, Jooss Natalie J, Bidzhekov Kiril, Santovito Donato, Moreno-Andrés Daniel, Jankowski Joachim, Biessen Erik A L, Döring Yvonne, Heemskerk Johan W M, Weber Christian, Kuijpers Marijke J E, van der Vorst Emiel P C
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52056 Aachen, Germany.
Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52056 Aachen, Germany.
Biomedicines. 2022 Apr 23;10(5):983. doi: 10.3390/biomedicines10050983.
Platelets are key regulators of haemostasis, making platelet dysfunction a major driver of thrombosis. Numerous processes that determine platelet function are influenced by microRNAs (miRs). MiR-26b is one of the highest-expressed miRs in healthy platelets, and its expression in platelets is changed in a diseased state. However, the exact effect of this miR on platelet function has not been studied yet. In this study, we made use of a whole-body knockout of in ApoE-deficient mice in order to determine its impact on platelet function, thrombus formation and platelet signalling both ex vivo and in vivo. We show that a whole-body deficiency of exacerbated platelet adhesion and aggregation ex vivo. Additionally, in vivo, platelets adhered faster, and larger thrombi were formed in mice lacking miR-26b. Moreover, isolated platelets from miR-26b-deficient mice showed a hyperactivated Src and EGFR signalling. Taken together, we show here for the first time that miR-26b attenuates platelet adhesion and aggregation, possibly through Src and EGFR signalling.
血小板是止血的关键调节因子，使得血小板功能障碍成为血栓形成的主要驱动因素。众多决定血小板功能的过程受到微小RNA（miR）的影响。MiR-26b是健康血小板中表达量最高的miR之一，其在血小板中的表达在疾病状态下会发生改变。然而，这种miR对血小板功能的确切影响尚未得到研究。在本研究中，我们利用ApoE缺陷小鼠的全身敲除模型，以确定其对体外和体内血小板功能、血栓形成及血小板信号传导的影响。我们发现，全身缺乏该miR会在体外加剧血小板的黏附和聚集。此外，在体内，缺乏miR-26b的小鼠体内血小板黏附更快，形成的血栓更大。而且，从miR-26b缺陷小鼠分离出的血小板显示出Src和EGFR信号的过度激活。综上所述，我们首次在此表明，miR-26b可能通过Src和EGFR信号传导减弱血小板的黏附和聚集。
