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Blood：血流剪切应力促进内皮细胞释放RNA介导侧支动脉形成

2019-09-10 MedSci MedSci原创

剪切应力内皮细胞eRNA动脉形成白细胞募集
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血管系统中的流体剪切应力是旁路自然生长的驱动力，是抵消闭塞性血管疾病(如中风或心肌梗死)的有害后果的一种基本的内源性机制。这一过程被称为动脉形成，它依赖于白细胞的局部聚集，而白细胞为已有的侧支动脉提供生长因子，促进其生长。虽然已经鉴定出几种机制蛋白，但导致局部白细胞募集的一系列机制转导事件仍不明确。在小鼠动脉形成(股动脉结扎处理)模型中，Manuel Lasch等人发现流体剪切应力增加时，内皮细胞

血管系统中的流体剪切应力是旁路自然生长的驱动力，是抵消闭塞性血管疾病(如中风或心肌梗死)的有害后果的一种基本的内源性机制。这一过程被称为动脉形成，它依赖于白细胞的局部聚集，而白细胞为已有的侧支动脉提供生长因子，促进其生长。虽然已经鉴定出几种机制蛋白，但导致局部白细胞募集的一系列机制转导事件仍不明确。

在小鼠动脉形成(股动脉结扎处理)模型中，Manuel Lasch等人发现流体剪切应力增加时，内皮细胞会释放RNA，而予以RNase抑制剂阻断血浆RNase的可改善灌注恢复。相反，用牛胰腺RNase A或人重组RNase1处理会干扰白细胞的募集和侧支动脉的生长。

本研究结果表明，细胞外RNA (eRNA)通过血管内皮生长因子受体2 (VEGFR2)调节白细胞的募集 ，这一点在小鼠提睾肌炎症模型的玻璃体内显微研究中得到了证实。此外，研究人员还发现剪切应力引起的血管性血友病因子(vWF)释放依赖于VEGFR2。阻断VEGFR2、应用RNase或vWF缺乏会干扰血小板-中性粒细胞的聚集，而血小板-中性粒细胞聚集对动脉形成的炎症过程至关重要。

综上所述，本结果表明在剪切应力作用下，内皮细胞释放eRNA。这种细胞外核酸，通过诱导vWF的释放在信号转导过程中发挥关键作用，从而启动了对动脉形成的必不可少的多步骤炎症过程。

原始出处：

Manuel Lasch，et al.Extracellular RNA released due to shear stress controls natural bypass growth by mediating mechanotransduction. Blood 2019 ：blood.2019001392； doi： https：//doi.org/10.1182/blood.2019001392

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    2019-11-26 jiadan198782

    #侧支动脉#

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  2. [GetPortalCommentsPageByObjectIdResponse(id=1944028, encodeId=a27a194402851, content=<a href='/topic/show?id=887126954da' target=_blank style='color:#2F92EE;'>#侧支动脉#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26954, encryptionId=887126954da, topicName=侧支动脉)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b70c362, createdName=jiadan198782, createdTime=Tue Nov 26 04:32:00 CST 2019, time=2019-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1928356, encodeId=a593192835643, content=<a href='/topic/show?id=e00332e553d' target=_blank style='color:#2F92EE;'>#剪切应力#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32755, encryptionId=e00332e553d, topicName=剪切应力)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6c3a189, createdName=longqijun248, createdTime=Thu May 14 23:32:00 CST 2020, time=2020-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1591081, encodeId=fe8a1591081cd, content=<a href='/topic/show?id=ed574924e8c' target=_blank style='color:#2F92EE;'>#应力#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49247, encryptionId=ed574924e8c, topicName=应力)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=jiangjun073, createdTime=Thu Sep 12 11:32:00 CST 2019, time=2019-09-12, status=1, ipAttribution=)]
    2020-05-14 longqijun248

    #剪切应力#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1944028, encodeId=a27a194402851, content=<a href='/topic/show?id=887126954da' target=_blank style='color:#2F92EE;'>#侧支动脉#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26954, encryptionId=887126954da, topicName=侧支动脉)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b70c362, createdName=jiadan198782, createdTime=Tue Nov 26 04:32:00 CST 2019, time=2019-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1928356, encodeId=a593192835643, content=<a href='/topic/show?id=e00332e553d' target=_blank style='color:#2F92EE;'>#剪切应力#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32755, encryptionId=e00332e553d, topicName=剪切应力)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6c3a189, createdName=longqijun248, createdTime=Thu May 14 23:32:00 CST 2020, time=2020-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1591081, encodeId=fe8a1591081cd, content=<a href='/topic/show?id=ed574924e8c' target=_blank style='color:#2F92EE;'>#应力#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49247, encryptionId=ed574924e8c, topicName=应力)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=jiangjun073, createdTime=Thu Sep 12 11:32:00 CST 2019, time=2019-09-12, status=1, ipAttribution=)]
    2019-09-12 jiangjun073

    #应力#

    0