Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease.
Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease.
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川崎病中血小板衍生的 microRNA-223 通过靶向 ICAM-1 减弱 TNF-α 诱导的单核细胞对动脉内皮的粘附
DOI：
10.3389/fimmu.2022.922868
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
川崎病 (KD) 是一种急性血管炎，可能导致冠状动脉永久性损伤，但病因不明。内皮细胞 (EC) 功能障碍和血小板过度活跃是 KD 的标志。血小板参与内皮功能障碍的发生。已发现血小板微粒 (PMP) 转移的 MiR-223 参与脓毒症中内皮细胞的功能调节。然而，血小板衍生的 miR-223 在川崎病中内皮功能障碍中的作用尚未得到研究。我们试图研究血小板衍生的 miR-223 在 KD 血管病变的内皮功能障碍中的作用。该研究随机招募了 45 名急性 KD 患者和 45 名匹配的对照者。当与人冠状动脉内皮细胞（HCAEC）共培养时，具有较高水平miR-223的KD血小板被整合到HCAEC中，导致miR-223的水平转移。使用与 HCAEC 共培养的等量血液中的 KD 血小板、PMP 和血小板释放物，我们发现 HCAEC 中 miR-223 表达增加主要来自 KD 血小板，而不是 PMP 或血小板释放物中的游离 miRNA。 KD 血小板来源的 miR-223 减弱 HCAEC 中 TNF-α 诱导的细胞间细胞粘附分子 1 (ICAM-1) 的表达。 KD 血小板衍生的 miR-223 也抑制单核细胞对 HCAEC 的粘附。在体内，使用血小板特异性miR-223敲除（PF4-cre：miR-223flox/flox）C57BL/6小鼠和miR-223flox/flox C57BL/6小鼠。使用干酪乳杆菌细胞壁提取物 (LCWE) 建立 KD 小鼠模型，我们发现在 LCWE 注射的 PF4-cre: miR-223flox/flox 小鼠中，与对照组相比，血小板-miR-223 缺乏会加剧腹主动脉内侧增厚，ICAM-1 表达增加，同时 CD45+ 炎症细胞浸润内皮。 LCWE 注射 miR-223flox/flox 小鼠。血小板来源的 miR-223 的水平转移抑制 HCAEC 中 ICAM-1 的表达，这至少部分减弱白细胞粘附，从而减少 KD 血管炎中的内皮损伤
Kawasaki disease (KD) is an acute vasculitis that may result in permanent coronary artery damage with unknown etiology. Endothelial cell (EC) dysfunction and platelet hyperactivity are the hallmarks of KD. Platelets are involved in the development of endothelial dysfunction. MiR-223 transferred by platelet microparticles (PMPs) has been found to involve in the functional regulation of endothelial cells in sepsis. However, the role of platelet-derived miR-223 in endothelial dysfunction has not yet been investigated in KD. We seek to investigate the role of platelet-derived miR-223 in endothelial dysfunction of KD vasculopathy. Forty-five acute KD patients and 45 matched controls were randomly recruited in the study. When co-cultured with human coronary artery endothelial cells (HCAECs), KD platelets with higher levels of miR-223 were incorporated into HCAECs, resulting in the horizontal transfer of miR-223. Using KD platelets, PMPs, and platelet-releasate from the same amount of blood co-cultured with HCAECs, we found the increased expression of miR-223 in HCAECs was primarily derived from KD platelets, rather than PMPs or free miRNAs from platelet- releasate. KD platelet-derived miR-223 attenuated TNF-α induced intercellular cell adhesion molecule-1 (ICAM-1) expression in HCAECs. KD platelet-derived miR-223 also suppressed the monocyte adhesion to HCAECs. In vivo, platelet-specific miR-223 knockout (PF4-cre: miR-223flox/flox) C57BL/6 mice and miR-223flox/flox C57BL/6 mice were used. Using Lactobacillus casei cell wall extract (LCWE) to establish KD murine model, we showed that in LCWE-injected PF4-cre: miR-223flox/flox mice, deficiency of platelet-miR-223 exacerbates the medial thickening of the abdominal aorta, increased ICAM-1 expression with concomitant CD45+ inflammatory cells infiltration into the endothelium compared to LCWE-injected miR-223flox/flox mice. The horizontal transfer of platelet-derived miR-223 suppresses the expression of ICAM-1 in HCAECs, which at least in part attenuates leukocyte adhesion, thereby reducing endothelial damage in KD vasculitis
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DOI：
10.1161/atvbaha.115.306475
发表时间：
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