Circulation:胆固醇流出通路可抑制炎症小体激活、坏死和动脉粥样硬化

2018-09-01 MedSci MedSci原创

CANTOS试验(研究康纳单抗抗炎性血栓预后)显示,白介素(IL)-1β的拮抗剂可减轻有心肌梗死病史患者的冠心病,同时可减少全身性炎症,提示调控IL-1β分泌的信号通路可增加心血管风险。胆固醇积累时,骨髓细胞可通过NLRP3炎症小体产生IL-1β和IL-18,但NLRP3炎症小体激活与动脉粥样硬化形成的关联尚不明确。胆固醇转运体ATP结合盒A1/G1(ABCA1/G1)介导胆固醇形成高密度脂蛋白,

CANTOS试验(研究康纳单抗抗炎性血栓预后)显示,白介素(IL)-1β的拮抗剂可减轻有心肌梗死病史患者的冠心病,同时可减少全身性炎症,提示调控IL-1β分泌的信号通路可增加血管风险。胆固醇积累时,骨髓细胞可通过NLRP3炎症小体产生IL-1β和IL-18,但NLRP3炎症小体激活与动脉粥样硬化形成的关联尚不明确。胆固醇转运体ATP结合盒A1/G1(ABCA1/G1)介导胆固醇形成高密度脂蛋白,骨髓细胞Abca1/g1缺陷可导致胆固醇积累。

为探究炎症小体激活与动脉粥样硬化之间的关联机制,研究人员采用髓细胞Abca1/g1缺陷的小鼠和伴随炎症小体成分Nlrp3或Caspase-1/11缺陷的小鼠,采集这些小鼠的骨髓移植到Ldlr-/-小鼠,高脂饮食喂养。

髓细胞Abca1/g1缺陷使Ldlr-/-小鼠血浆IL-18水平增加,并诱导脾细胞分泌IL-1β和IL-18,此效应可被Nlrp3或Caspase-1/11缺陷逆转,提示NLRP3炎症小体激活。Nlrp3或Caspase-1/11缺陷可减少髓细胞Abca1/g1缺陷小鼠的动脉粥样硬化病损大小。髓细胞Abca1/g1缺陷不仅可增强脾单核细胞和巨噬细胞的caspase-1分裂,还可增强中性粒细胞的caspase-1分裂,此外,还可显著增加动脉粥样硬化斑块中的中心粒细胞积累和中性粒细胞胞外诱捕形成,并可被Nlrp3或Caspase-1/11缺陷逆转,表明炎症小体激活可促进动脉粥样硬化斑块中的中性粒细胞招募和中性粒细胞胞外诱捕形成。系统炎症似乎可间接介导上述效应,导致中性粒细胞在斑块中激活积累。髓细胞Abca1/g1缺陷还可激活非典型的炎症小体,增加对脂多糖诱导性死亡的敏感性。Tangier疾病(高密度脂蛋白缺乏)患者,在ABCA1上携带功能丧失性突变,骨髓胆固醇含量增高,血浆IL-1β和IL-18水平显著升高。

综上所述,胆固醇在骨髓细胞中积累可激活NLRP3炎症小体,进而增加动脉粥样硬化斑块中的中性粒细胞积累和中性粒细胞胞外诱捕形成。


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    2018-09-03 liumin1987

    嗯嗯,学习了。

    0

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    2018-09-03 millore
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    2018-09-01 1e1b8538m79(暂无匿称)

    不错的文章值得拥有哦

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1809342, encodeId=538a180934291, content=<a href='/topic/show?id=5b6d8345911' target=_blank style='color:#2F92EE;'>#胆固醇流出通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83459, encryptionId=5b6d8345911, topicName=胆固醇流出通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Fri Mar 01 02:59:00 CST 2019, time=2019-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1944552, encodeId=3b731944552b1, 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=21, 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=Sun Aug 18 12:59:00 CST 2019, time=2019-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342471, encodeId=f50e3424e1f6, content=嗯嗯,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/07/16/3b24606172648eea459125cb74754afe.jpg, createdBy=6c022216608, createdName=liumin1987, createdTime=Mon Sep 03 15:40:06 CST 2018, time=2018-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1362905, encodeId=968513629051f, content=<a href='/topic/show?id=b723414321c' target=_blank style='color:#2F92EE;'>#坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41432, encryptionId=b723414321c, topicName=坏死)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Mon Sep 03 11:59:00 CST 2018, time=2018-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342162, encodeId=3a483421629a, content=不错的文章值得拥有哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Sat Sep 01 23:03:51 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342155, encodeId=a6673421557e, content=了解一下,谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Sat Sep 01 22:12:09 CST 2018, time=2018-09-01, status=1, ipAttribution=)]
    2018-09-01 天地飞扬

    了解一下,谢谢分享!

    0

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