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Circulation:连接COX-2抑制剂&心血管功能障碍的桥梁---ADMA(一氧化氮合成酶抑制剂)

2014-12-17 MedSci MedSci原创

非甾体类抗炎药COX-2抑制剂能发挥抗炎作用,但是,COX-2抑制剂会打破体内促血栓和抗血栓之间的平衡,从而引起心血管副作用,主要是心肌梗死,血栓和/或动脉粥样硬化的增加。 COX-2调节肾功能的机制以及COX-2在肾脏和心血管组织中的关联并未被明确,COX-2对前列环素调节和其非甾体类抗炎药的心血管副作用备受争议,而且并没有生物标记物用于研究机非甾体类抗炎药诱导产生的心血管风险。伦敦帝国理

非甾体类抗炎药COX-2抑制剂能发挥抗炎作用,但是,COX-2抑制剂会打破体内促血栓和抗血栓之间的平衡,从而引起心血管副作用,主要是心肌梗死,血栓和/或动脉粥样硬化的增加。

COX-2调节肾功能的机制以及COX-2在肾脏和心血管组织中的关联并未被明确,COX-2对前列环素调节和其非甾体类抗炎药的心血管副作用备受争议,而且并没有生物标记物用于研究机非甾体类抗炎药诱导产生的心血管风险。伦敦帝国理工学院Blerina Ahmetaj-Shala博士及其同事主要研究COX-2在肾脏中通过脉管系统对心血管副作用的调节机制,以及研究非甾体类抗炎药诱导心血管风险的生物标记物ADMA。其研究成果发表在12月的Circulation杂志上。

环氧化酶(COX)抑制剂相关的心血管副反应是临床上主要被关注的对象。COX-2在肾髓质中表达,其抑制剂会导致液体潴留以及血压升高。然而,COX-2抑制剂和心血管事件相联系的机制仍然是未知的,而且并没有生物标志物被用于检测两者的关系。

方法和结果:

COX-2缺失(COX-2-/-)的野生型鼠组织转录组分析显示,心脏和大动脉中有1个基因改变,但在肾髓质中有大于1000个基因发生了改变,包括调节内源性一氧化氮合酶抑制剂二甲基精氨酸(ADMA)和L-单甲基精氨酸(L-NMMA);COX-2-/-鼠ADMA和L-NMMA血浆水平升高,内源性一氧化氮应答降低。这些基因和甲基精氨酸在前列环素受体缺失(IP-/-)鼠中并不是相似地改变。野生型鼠或使用COX-2抑制剂的志愿者显示血浆ADMA升高。内源性一氧化氮具有心脏保护作用,能够减少血栓以及动脉粥样硬化。ADMA升高和心血管疾病存在一定的联系。研究将ADMA作为生物标志物,在未使用非甾体类抗炎药条件下作为肾COX-2抑制剂和全身血管功能障碍之间的桥梁。
      
结论:

研究明确了内源性一氧化氮合成酶抑制剂ADMA可以作为生物标志物,以及作为肾COX-2抑制剂和全身血管功能障碍之间的桥梁。

原始出处

Ahmetaj-Shala B, Kirkby NS, Knowles R, Al'Yamani M, Mazi S, Wang Z, Tucker AT, Mackenzie L, Armstrong PC, Nusing RM, Tomlinson JA, Warner TD, Lieper J, Mitchell JA. Evidence That Links Loss of Cyclo-Oxygenase-2 With Increased Asymmetric Dimethylarginine: Novel Explanation of Cardiovascular Side Effects Associated With Anti-inflammatory Drugs. Circulation. 2014. Dec 9

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    2015-02-09 jklm09
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1851211, encodeId=7a791851211d1, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Feb 09 23:43:00 CST 2015, time=2015-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995470, encodeId=aaf119954e033, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Wed May 06 19:43:00 CST 2015, time=2015-05-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703406, encodeId=c9491e03406c9, content=<a href='/topic/show?id=9b4751449d' target=_blank style='color:#2F92EE;'>#COX-2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5144, encryptionId=9b4751449d, topicName=COX-2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=387330501690, createdName=chenlianhui, createdTime=Tue Sep 29 01:43:00 CST 2015, time=2015-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1993113, encodeId=6aca199311375, content=<a href='/topic/show?id=c0252000c9' target=_blank style='color:#2F92EE;'>#ADMA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2000, 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target=_blank style='color:#2F92EE;'>#一氧化氮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19358, encryptionId=96fd19358fa, topicName=一氧化氮)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKjqGDO7icVKUiaT7urgwXvnvzWtp0fMFU46Xfib8oavFKygiaWtibXReS6ZUh3PImsNicGAwTO5HXxoicnA/132, createdBy=ee262500130, createdName=ms7474195563676018, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1421014, encodeId=c62e14210146e, content=<a href='/topic/show?id=09d33294eb8' target=_blank style='color:#2F92EE;'>#功能障碍#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32947, encryptionId=09d33294eb8, topicName=功能障碍)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b3493649807, createdName=naiwu78, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511961, encodeId=7074151196172, content=<a href='/topic/show?id=da82895e077' target=_blank style='color:#2F92EE;'>#血管功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89570, encryptionId=da82895e077, topicName=血管功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a8810427189, createdName=1249859em41(暂无昵称), createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533670, encodeId=493e15336e021, content=<a href='/topic/show?id=34e6514391' target=_blank style='color:#2F92EE;'>#COX-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5143, encryptionId=34e6514391, topicName=COX-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=544412475251, createdName=手留余香, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1851211, encodeId=7a791851211d1, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Feb 09 23:43:00 CST 2015, time=2015-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995470, encodeId=aaf119954e033, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Wed May 06 19:43:00 CST 2015, time=2015-05-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703406, encodeId=c9491e03406c9, content=<a href='/topic/show?id=9b4751449d' target=_blank style='color:#2F92EE;'>#COX-2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5144, encryptionId=9b4751449d, topicName=COX-2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=387330501690, createdName=chenlianhui, createdTime=Tue Sep 29 01:43:00 CST 2015, time=2015-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1993113, encodeId=6aca199311375, content=<a href='/topic/show?id=c0252000c9' target=_blank style='color:#2F92EE;'>#ADMA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2000, 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target=_blank style='color:#2F92EE;'>#一氧化氮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19358, encryptionId=96fd19358fa, topicName=一氧化氮)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKjqGDO7icVKUiaT7urgwXvnvzWtp0fMFU46Xfib8oavFKygiaWtibXReS6ZUh3PImsNicGAwTO5HXxoicnA/132, createdBy=ee262500130, createdName=ms7474195563676018, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1421014, encodeId=c62e14210146e, content=<a href='/topic/show?id=09d33294eb8' target=_blank style='color:#2F92EE;'>#功能障碍#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32947, encryptionId=09d33294eb8, topicName=功能障碍)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b3493649807, createdName=naiwu78, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511961, encodeId=7074151196172, content=<a href='/topic/show?id=da82895e077' target=_blank style='color:#2F92EE;'>#血管功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89570, encryptionId=da82895e077, topicName=血管功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a8810427189, createdName=1249859em41(暂无昵称), createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533670, encodeId=493e15336e021, content=<a href='/topic/show?id=34e6514391' target=_blank style='color:#2F92EE;'>#COX-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5143, encryptionId=34e6514391, topicName=COX-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=544412475251, createdName=手留余香, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=)]
    2015-05-05 anminleiryan
  6. 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target=_blank style='color:#2F92EE;'>#一氧化氮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19358, encryptionId=96fd19358fa, topicName=一氧化氮)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKjqGDO7icVKUiaT7urgwXvnvzWtp0fMFU46Xfib8oavFKygiaWtibXReS6ZUh3PImsNicGAwTO5HXxoicnA/132, createdBy=ee262500130, createdName=ms7474195563676018, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1421014, encodeId=c62e14210146e, content=<a href='/topic/show?id=09d33294eb8' target=_blank style='color:#2F92EE;'>#功能障碍#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32947, encryptionId=09d33294eb8, topicName=功能障碍)], attachment=null, authenticateStatus=null, 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  7. 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target=_blank style='color:#2F92EE;'>#一氧化氮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19358, encryptionId=96fd19358fa, topicName=一氧化氮)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKjqGDO7icVKUiaT7urgwXvnvzWtp0fMFU46Xfib8oavFKygiaWtibXReS6ZUh3PImsNicGAwTO5HXxoicnA/132, createdBy=ee262500130, createdName=ms7474195563676018, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1421014, encodeId=c62e14210146e, content=<a href='/topic/show?id=09d33294eb8' target=_blank style='color:#2F92EE;'>#功能障碍#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32947, encryptionId=09d33294eb8, topicName=功能障碍)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b3493649807, createdName=naiwu78, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511961, encodeId=7074151196172, content=<a href='/topic/show?id=da82895e077' target=_blank style='color:#2F92EE;'>#血管功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89570, encryptionId=da82895e077, topicName=血管功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a8810427189, createdName=1249859em41(暂无昵称), createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533670, encodeId=493e15336e021, content=<a href='/topic/show?id=34e6514391' target=_blank style='color:#2F92EE;'>#COX-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5143, encryptionId=34e6514391, topicName=COX-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=544412475251, createdName=手留余香, createdTime=Fri Dec 19 06:43:00 CST 2014, time=2014-12-19, status=1, ipAttribution=)]
  8. 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  9. 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