心血管

订阅

MedSci主页 / 所有栏目 / 心血管

Circulation：抑制SAHH可p66shc介导的氧化应激通路诱导内皮细胞功能障碍

2019-05-16 MedSci MedSci原创

S-腺苷同型半胱氨酸SAHHp66shc
关注

高水平的S-腺苷同型半胱氨酸(SAH，同型半胱氨酸的前体)与心血管疾病的风险以及动脉粥样硬化的发生发展均呈正相关。但SAH在内皮功能障碍中的作用尚不明确。给载脂蛋白E缺陷(apoE-/-)小鼠饮食中添加SAH水解酶(SAHH)抑制剂腺苷二醛或静脉注射表达SAHH shRNA的逆转录病毒。此外，还建立杂合敲除SAHH基因（SAHH+/-）的小鼠模型，用于升高血浆SAH浓度，检测SAH在动脉内皮功能障

高水平的S-腺苷同型半胱氨酸(SAH，同型半胱氨酸的前体)与心血管疾病的风险以及动脉粥样硬化的发生发展均呈正相关。但SAH在内皮功能障碍中的作用尚不明确。

给载脂蛋白E缺陷(apoE-/-)小鼠饮食中添加SAH水解酶(SAHH)抑制剂腺苷二醛或静脉注射表达SAHH shRNA的逆转录病毒。此外，还建立杂合敲除SAHH基因（SAHH+/-）的小鼠模型，用于升高血浆SAH浓度，检测SAH在动脉内皮功能障碍中的作用。

在SAHH+/-小鼠和予以饮食处理或注射了SAHH shRNA的apoE-/-小鼠中，血浆SAH浓度升高。经乙酰胆碱治疗后，SAHH+/-小鼠或SAHH抑制的apoE-/-小鼠均表现为内皮依赖性的血管舒张受损和NO生物利用度降低；注射内皮NO合成抑制剂可完全消除上述效应。

此外，SAHH抑制可减少小鼠和人动脉内皮细胞中活性氧的产生和p66shc的表达。在高SAH小鼠中，抗氧化剂和p66shc siRNA可阻断SAHH抑制诱导的内皮细胞活性氧生成，并减轻内皮细胞舒缩反应损伤。而且，抑制SAHH可诱导p66shc基因启动子低甲基化，抑制DNA甲基转移酶1的表达。通过转染腺病毒过表达DNA甲基转移酶1可有效废除SAHH抑制诱导的p66shc表达上调。

最后，血浆SAH浓度与血流介导的p66shc基因启动子的扩增和低甲基化呈负相关，与冠心病患者和健康对照组的氧化应激水平呈正相关。

综上所述，本研究表明抑制SAHH可通过表观遗传上调p66shc介导的氧化应激通路升高血浆SAH浓度，诱导内皮细胞功能障碍；为SAH相关的内皮损伤机制的研究提供了新的分子视角。

原始出处：

Yunjun Xiao，et al. Inhibition of S-Adenosylhomocysteine Hydrolase Induces Endothelial Dysfunction via Epigenetic Regulation of p66shc-Mediated Oxidative Stress Pathway. Circulation. 7 May 2019. https：//doi.org/10.1161/CIRCULATIONAHA.118.036336. 2019；139：2260–2277

本文系梅斯医学（MedSci）原创编译，转载需授权！

版权声明：
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料，版权均属于梅斯医学所有。非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章，或“梅斯号”自媒体发布的文章，仅系出于传递更多信息之目的，本站仅负责审核内容合规，其内容不代表本站立场，本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1421231, encodeId=b13114212310c, 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=27, 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=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1445283, encodeId=d2731445283ef, content=<a href='/topic/show?id=61e74928629' target=_blank style='color:#2F92EE;'>#应激#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49286, encryptionId=61e74928629, topicName=应激)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79df5138909, createdName=ms1260584454294838, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1460311, encodeId=19e2146031166, content=<a href='/topic/show?id=de5015845be' target=_blank style='color:#2F92EE;'>#SAH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15845, encryptionId=de5015845be, topicName=SAH)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f9f06287396, createdName=zexyw03, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586838, encodeId=574c158683894, content=<a href='/topic/show?id=a6d1e7821de' target=_blank style='color:#2F92EE;'>#细胞功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77821, encryptionId=a6d1e7821de, topicName=细胞功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ec517387980, createdName=般若傻瓜, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=)]
    2019-05-18 naiwu78

    #功能障碍#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1421231, encodeId=b13114212310c, 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=27, 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=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1445283, encodeId=d2731445283ef, content=<a href='/topic/show?id=61e74928629' target=_blank style='color:#2F92EE;'>#应激#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49286, encryptionId=61e74928629, topicName=应激)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79df5138909, createdName=ms1260584454294838, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1460311, encodeId=19e2146031166, content=<a href='/topic/show?id=de5015845be' target=_blank style='color:#2F92EE;'>#SAH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15845, encryptionId=de5015845be, topicName=SAH)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f9f06287396, createdName=zexyw03, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586838, encodeId=574c158683894, content=<a href='/topic/show?id=a6d1e7821de' target=_blank style='color:#2F92EE;'>#细胞功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77821, encryptionId=a6d1e7821de, topicName=细胞功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ec517387980, createdName=般若傻瓜, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=)]
    2019-05-18 ms1260584454294838

    #应激#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1421231, encodeId=b13114212310c, 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=27, 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=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1445283, encodeId=d2731445283ef, content=<a href='/topic/show?id=61e74928629' target=_blank style='color:#2F92EE;'>#应激#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49286, encryptionId=61e74928629, topicName=应激)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79df5138909, createdName=ms1260584454294838, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1460311, encodeId=19e2146031166, content=<a href='/topic/show?id=de5015845be' target=_blank style='color:#2F92EE;'>#SAH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15845, encryptionId=de5015845be, topicName=SAH)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f9f06287396, createdName=zexyw03, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586838, encodeId=574c158683894, content=<a href='/topic/show?id=a6d1e7821de' target=_blank style='color:#2F92EE;'>#细胞功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77821, encryptionId=a6d1e7821de, topicName=细胞功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ec517387980, createdName=般若傻瓜, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=)]
    2019-05-18 zexyw03

    #SAH#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1421231, encodeId=b13114212310c, 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=27, 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=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1445283, encodeId=d2731445283ef, content=<a href='/topic/show?id=61e74928629' target=_blank style='color:#2F92EE;'>#应激#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49286, encryptionId=61e74928629, topicName=应激)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79df5138909, createdName=ms1260584454294838, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1460311, encodeId=19e2146031166, content=<a href='/topic/show?id=de5015845be' target=_blank style='color:#2F92EE;'>#SAH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15845, encryptionId=de5015845be, topicName=SAH)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f9f06287396, createdName=zexyw03, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586838, encodeId=574c158683894, content=<a href='/topic/show?id=a6d1e7821de' target=_blank style='color:#2F92EE;'>#细胞功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77821, encryptionId=a6d1e7821de, topicName=细胞功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ec517387980, createdName=般若傻瓜, createdTime=Sat May 18 12:06:00 CST 2019, time=2019-05-18, status=1, ipAttribution=)]
    2019-05-18 般若傻瓜

    #细胞功能#

    0