Sci Rep:晚期糖基化终产物通过HIF-1α/PDK4活化加速VSMC中的钙化并抑制葡萄糖代谢

2018-09-20 MedSci MedSci原创

动脉介质钙化与糖尿病有关。以前的研究表明,晚期糖基化终产物(AGEs)是造成血管平滑肌细胞(VSMC)钙化的原因,但其潜在的机制尚不清楚。缺氧诱导因子-1α(HIF-1α)是缺氧期间的主要因子之一,丙酮酸脱氢酶激酶4(PDK4)是细胞代谢转变中重要的线粒体基质酶,均在VSMC钙化中报道。本研究调查了HIF-1α、PDK4和AGEs诱导的血管钙化之间的潜在联系。结果显示,AGEs以剂量依赖性方式升高

动脉介质钙化与糖尿病有关。以前的研究表明,晚期糖基化终产物(AGEs)是造成血管平滑肌细胞(VSMC)钙化的原因,但其潜在的机制尚不清楚。缺氧诱导因子-1α(HIF-1α)是缺氧期间的主要因子之一,丙酮酸脱氢酶激酶4(PDK4)是细胞代谢转变中重要的线粒体基质酶,均在VSMC钙化中报道。

本研究调查了HIF-1α、PDK4和AGEs诱导的血管钙化之间的潜在联系。结果显示,AGEs以剂量依赖性方式升高HIF-1α和PDK4的表达水平,并且在24小时达到最大。AGEs暴露后,两种重要的HIF-1α调节基因,血管内皮生长因子A(VEGFA)和葡萄糖转运蛋白1(GLUT-1)的表达显著增加。HIF-1α的稳定化或核转位增加PDK4的表达。钙含量、碱性磷酸酶(ALP)活性和runt相关转录因子2(RUNX2)表达水平和通过茜素红S染色评估确定PDK4抑制减弱AGEs诱导的VSMC钙化。此外,在AGEs诱导的VSMC钙化期间,葡萄糖消耗、乳酸产生、葡萄糖代谢的关键酶和氧消耗率(OCR)降低。

总之,该研究表明,AGEs部分通过HIF-1α/PDK4通路加速血管钙化并抑制葡萄糖代谢。

原始出处:

Yi Zhu, Wen-Qi Ma, Xi-Qiong Han, et al., Advanced glycation end products accelerate calcification in VSMCs through HIF-1α/PDK4 activation and suppress glucose metabolism. Sci Rep. 2018; 8: 13730.

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    2019-08-20 ailian1212
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    2018-10-21 huhuaidong387
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    2018-09-22 lfyang
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    2018-09-22 zz70
  5. [GetPortalCommentsPageByObjectIdResponse(id=1704848, encodeId=a64f1e04848a1, content=<a href='/topic/show?id=f32e139595d' target=_blank style='color:#2F92EE;'>#PDK4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13959, encryptionId=f32e139595d, topicName=PDK4)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c06a30851040, createdName=ailian1212, createdTime=Tue Aug 20 16:28:00 CST 2019, time=2019-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1937874, encodeId=aa81193e8744e, content=<a href='/topic/show?id=e4281644634' target=_blank style='color:#2F92EE;'>#SMC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16446, encryptionId=e4281644634, topicName=SMC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Sun Oct 21 12:28:00 CST 2018, time=2018-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1318301, encodeId=9d091318301ae, content=<a href='/topic/show?id=b5dde6644b1' target=_blank style='color:#2F92EE;'>#糖基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76644, encryptionId=b5dde6644b1, topicName=糖基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43cb463, createdName=lfyang, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1360610, encodeId=490b136061082, content=<a href='/topic/show?id=16a6e66155b' target=_blank style='color:#2F92EE;'>#糖代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76615, encryptionId=16a6e66155b, topicName=糖代谢)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30f5146, createdName=zz70, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1522152, encodeId=1f8e15221524e, content=<a href='/topic/show?id=1b34881e59' target=_blank style='color:#2F92EE;'>#HIF-1α#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8817, encryptionId=1b34881e59, topicName=HIF-1α)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=847f11414102, createdName=changfy, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553653, encodeId=8b36155365373, content=<a href='/topic/show?id=abae8824611' target=_blank style='color:#2F92EE;'>#葡萄糖代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88246, encryptionId=abae8824611, topicName=葡萄糖代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=82e414392307, createdName=wfang550, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556036, encodeId=e6d115560361b, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=)]
    2018-09-22 changfy
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  7. [GetPortalCommentsPageByObjectIdResponse(id=1704848, encodeId=a64f1e04848a1, content=<a href='/topic/show?id=f32e139595d' target=_blank style='color:#2F92EE;'>#PDK4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13959, encryptionId=f32e139595d, topicName=PDK4)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c06a30851040, createdName=ailian1212, createdTime=Tue Aug 20 16:28:00 CST 2019, time=2019-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1937874, encodeId=aa81193e8744e, content=<a href='/topic/show?id=e4281644634' target=_blank style='color:#2F92EE;'>#SMC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16446, encryptionId=e4281644634, topicName=SMC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Sun Oct 21 12:28:00 CST 2018, time=2018-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1318301, encodeId=9d091318301ae, content=<a href='/topic/show?id=b5dde6644b1' target=_blank style='color:#2F92EE;'>#糖基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76644, encryptionId=b5dde6644b1, topicName=糖基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43cb463, createdName=lfyang, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1360610, encodeId=490b136061082, content=<a href='/topic/show?id=16a6e66155b' target=_blank style='color:#2F92EE;'>#糖代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76615, encryptionId=16a6e66155b, topicName=糖代谢)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30f5146, createdName=zz70, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1522152, encodeId=1f8e15221524e, content=<a href='/topic/show?id=1b34881e59' target=_blank style='color:#2F92EE;'>#HIF-1α#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8817, encryptionId=1b34881e59, topicName=HIF-1α)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=847f11414102, createdName=changfy, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553653, encodeId=8b36155365373, content=<a href='/topic/show?id=abae8824611' target=_blank style='color:#2F92EE;'>#葡萄糖代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88246, encryptionId=abae8824611, topicName=葡萄糖代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=82e414392307, createdName=wfang550, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556036, encodeId=e6d115560361b, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Sat Sep 22 09:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=)]
    2018-09-22 wrj0126