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Circulation：Krüppel样因子4调节Ch25h和LXR减轻动脉粥样硬化

2017-10-03 MedSci MedSci原创

Ch25hLXRKLF4动脉粥样硬化
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动脉粥样硬化是包括血管壁细胞（例如内皮细胞[ECs]）以及循环和驻留的免疫原性细胞（如单核细胞/巨噬细胞）在内的多种细胞参与的炎性疾病。作为肝脏X受体（LXR）的配体，SREBP2（甾醇调节元件结合蛋白2）的抑制剂，25-羟基胆固醇及其催化酶胆固醇-25-羟化酶（Ch25h）在调节细胞炎症状态中发挥着重要的作用，且在ECs和单核细胞/巨噬细胞中胆固醇的生物合成中发挥着重要作用。研究人员采用生物信息

动脉粥样硬化是包括血管壁细胞（例如内皮细胞[ECs]）以及循环和驻留的免疫原性细胞（如单核细胞/巨噬细胞）在内的多种细胞参与的炎性疾病。作为肝脏X受体（LXR）的配体，SREBP2（甾醇调节元件结合蛋白2）的抑制剂，25-羟基胆固醇及其催化酶胆固醇-25-羟化酶（Ch25h）在调节细胞炎症状态中发挥着重要的作用，且在ECs和单核细胞/巨噬细胞中胆固醇的生物合成中发挥着重要作用。

研究人员采用生物信息学分析方法研究RNA-测序数据，以鉴定由Krüppel样因子4（KLF4）调控的胆固醇氧化和外排基因。然后体外实验使用培养的ECs和巨噬细胞，体内实验使用具有Ch25h消融的小鼠来探究KLF4-Ch25h/LXR的动脉粥样硬化保护作用。

结果显示，血管保护性刺激通过KLF4增加Ch25h和LXR的表达。KLF4-Ch25h / LXR稳态轴通过抑制炎症起作用，ECs中炎症性活性的降低及促进巨噬细胞由M1到M2表型的转化证实了这点。载脂蛋白E - / - / Ch25h - / - 小鼠动脉粥样硬化增加进一步证明了KLF4-Ch25h / LXR轴在血管功能和疾病中的有益作用。

总之，该研究结果表明，KLF4激活Ch25h和LXR，从而促进ECs和巨噬细胞之间的协同作用，以防止动脉粥样硬化易感性。

原始出处：

Zhao Li, Marcy Martin, Jin Zhang, et al., Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility. Circulation. 2017;136:1315-1330, originally published August 9, 2017

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    2018-07-07 huangshifeng

    #粥样硬化#

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    2018-09-17 feather89

    #PE#

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    2017-10-05 tidiq

    #PEL#

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    2017-10-03 131****1460

    学习了受益匪浅

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    2017-10-03 1e0e5697m83(暂无匿称)

    henhao

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1944491, encodeId=bf77194449145, content=<a href='/topic/show?id=411de6300ad' target=_blank style='color:#2F92EE;'>#粥样硬化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76300, encryptionId=411de6300ad, topicName=粥样硬化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b30d401, createdName=huangshifeng, createdTime=Sat Jul 07 22:14:00 CST 2018, time=2018-07-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1726780, encodeId=4e2d1e2678083, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f06c33759375, createdName=feather89, createdTime=Mon Sep 17 10:14:00 CST 2018, time=2018-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1625825, encodeId=ff1c1625825d2, content=<a href='/topic/show?id=bc29140196e' target=_blank style='color:#2F92EE;'>#PEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14019, encryptionId=bc29140196e, topicName=PEL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=399320916411, createdName=tidiq, createdTime=Thu Oct 05 03:14:00 CST 2017, time=2017-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=250075, encodeId=cd9b2500e5a4, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Tue Oct 03 18:08:14 CST 2017, time=2017-10-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=250050, encodeId=492c25005089, content=henhao, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b10c1938054, createdName=1e0e5697m83(暂无匿称), createdTime=Tue Oct 03 17:35:33 CST 2017, time=2017-10-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=250020, encodeId=d004250020fa, content=学习了新的机制.谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Tue Oct 03 14:46:04 CST 2017, time=2017-10-03, status=1, ipAttribution=)]
    2017-10-03 惠映实验室

    学习了新的机制.谢谢

    0