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Diabetes：ADAMTS13缺陷会缩短实验性糖尿病小鼠的寿命

2018-07-08 MedSci MedSci原创

ADAMTS13糖尿病心律失常
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ADAMTS13，是一种血浆金属蛋白酶，可高效清除血栓性VWF多聚体；糖尿病患者的ADAMTS13活性多降低，是心血管事件的重要风险因素。Paola Cassis等人利用链脲霉素诱导的Adamts13-/-糖尿病小鼠模型，探究缺乏ADAMTS13对糖尿病相关的终末器官并发症的发展的影响。与野生型的糖尿病同窝小鼠相比，Adamts13-/-小鼠寿命缩短。此外，小鼠死亡与可检测出到的血栓事件的发生无关

ADAMTS13，是一种血浆金属蛋白酶，可高效清除血栓性VWF多聚体；糖尿病患者的ADAMTS13活性多降低，是心血管事件的重要风险因素。Paola Cassis等人利用链脲霉素诱导的Adamts13-/-糖尿病小鼠模型，探究缺乏ADAMTS13对糖尿病相关的终末器官并发症的发展的影响。

与野生型的糖尿病同窝小鼠相比，Adamts13-/-小鼠寿命缩短。此外，小鼠死亡与可检测出到的血栓事件的发生无关。缺乏ADAMTS13可明显增加糖尿病小鼠在多巴酚丁胺刺激下发生室性心律失常的倾向。Adamts13-/-小鼠的心肌细胞表现为心室缝隙连接蛋白43（Cx43）的分布异常、Ca2+/钙调蛋白依赖性激酶II（CaMKII）的磷酸化增强，进而导致CaMKII诱导的Ca2+内流外排紊乱，最终导致心律失常。

在体外，血小板反应蛋白（TSP1）以旁分泌方式促进小鼠HL-1心肌细胞CaMKII磷酸化，而ADMATS13充当TSP1诱导的CaMKII激活的抑制因子。

总而言之，ADAMTS13缺陷或可通过增强心肌细胞的CaMKII磷酸化促进糖尿病动物发生致死性的心律失常。本研究揭示了ADAMTS13除了抗血栓活性之外的新功能。

原始出处：

Paola Cassis， et al. ADAMTS13 Deficiency Shortens the Lifespan of Mice with Experimental Diabetes. Diabetes  2018 Jul；  db171508.  https：//doi.org/10.2337/db17-1508

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    #Diabetes#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1760747, encodeId=5d9a1e60747d3, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sat Oct 06 04:18:00 CST 2018, time=2018-10-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1638689, encodeId=f49a163868938, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Fri Aug 03 16:18:00 CST 2018, time=2018-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1738407, encodeId=538d1e38407b1, content=<a href='/topic/show?id=ec1e19404d' target=_blank style='color:#2F92EE;'>#ADAMTS13#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1940, encryptionId=ec1e19404d, topicName=ADAMTS13)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d90e34423140, createdName=124987e8m18暂无昵称, createdTime=Mon Nov 19 13:18:00 CST 2018, time=2018-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2040724, encodeId=418e2040e24b4, content=<a href='/topic/show?id=5887461103d' target=_blank style='color:#2F92EE;'>#实验性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46110, encryptionId=5887461103d, topicName=实验性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3c5e117, createdName=lujian, createdTime=Mon Aug 20 17:18:00 CST 2018, time=2018-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902090, encodeId=fd1f190209079, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5917, encryptionId=c097591ed5, topicName=Diabetes)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0045169, createdName=木头人513, createdTime=Wed Jun 19 22:18:00 CST 2019, time=2019-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1264660, encodeId=1e1d12646604e, content=<a href='/topic/show?id=150f19229c' target=_blank style='color:#2F92EE;'>#ADA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1922, encryptionId=150f19229c, topicName=ADA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Tue Jul 10 06:18:00 CST 2018, time=2018-07-10, status=1, ipAttribution=)]
    2018-07-10 般若傻瓜

    #ADA#

    0