Circulation:肺动脉高压:新内膜形成闭塞的“罪魁祸首”

2020-10-26 MedSci原创 MedSci原创

肺动脉高压(PAH)是一种致命疾病,其特征是明显的血管重构,其中由于内膜增厚和新内膜病变闭塞导致肺动脉狭窄,进而导致肺血管阻力增加和右心衰竭。针对新内膜的疗法或可代表PAH治疗的重要进展;然而,目前我

肺动脉高压(PAH)是一种致命疾病,其特征是明显的血管重构,其中由于内膜增厚和新内膜病变闭塞导致肺动脉狭窄,进而导致肺血管阻力增加和右心衰竭。针对新内膜的疗法或可代表PAH治疗的重要进展;然而,目前我们对驱动新内膜形成的细胞事件以及调控它们的分子机制尚未完全了解。

该研究在肺动脉高压的慢性炎症小鼠模型中全面分析了肺动脉逐步重构的特征。

慢性炎症诱发小鼠肺动脉高压

该模型展示了从右心室压力升高→内膜增厚→新内膜病变形成→弹性蛋白断裂→血管周围炎症一些列过程的病理特征。而且还通过多种研究手段定义了血管重构各个阶段的细胞行为,并确定了新内膜形成所需的信号通路。

增厚内膜和新内膜均起于平滑肌细胞

新内膜起于平滑肌细胞(SMC),而非内皮细胞。内膜SMC广泛增殖使内膜增厚,随后,少量SMC参与形成新内膜。这些新内膜基础细胞随后大量克隆性扩增以形成闭塞性新内膜损伤。

Notch3表达平滑肌细胞是新内膜起源

正常的肺动脉SMC群体是异质性的,研究人员将Notch3标记的少数SMC亚群确定为主要的新内膜细胞。Notch信号是选择新内膜基础细胞特别需要的,Notch抑制可显著降低肺动脉高压动物模型的肺动脉压。

动脉高压小鼠出现人特发性肺动脉高压的多种病理特征

该研究首次采用由非遗传因素驱动的肺动脉高压小鼠模型,揭示了参与肺动脉内膜增厚和新内膜形成的不同细胞和分子机制,并突出了肺动脉SMC中的新型转录、行为和致病异质性。

肺动脉高压病变模式图

在该模型中,慢性炎症足以诱导产生人PAH的特征性血管病变和生理特征。该研究可为开辟治疗PAH的新途径提供线索。

原始出处:

Lea C. Steffes, et al. A Notch3-Marked Subpopulation of Vascular Smooth Muscle Cells Is the Cell of Origin for Occlusive Pulmonary Vascular Lesions. Circulation. 2020;142:1545–1561

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    2020-10-29 Lexi

    慢性炎症足以诱导产生人PAH的特征性血管病变和生理特征。该研究可为开辟治疗PAH的新途径提供线索。

    0

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    2020-10-27 Lexi

    该研究在肺动脉高压的慢性炎症小鼠模型中全面分析了肺动脉逐步重构的特征。

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1925348, encodeId=b0fd192534838, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Sun Dec 13 02:24:59 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1708611, encodeId=161e1e0861162, content=<a href='/topic/show?id=4c2d3051535' target=_blank style='color:#2F92EE;'>#内膜#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30515, encryptionId=4c2d3051535, topicName=内膜)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=730431558473, createdName=12498974m61暂无昵称, createdTime=Mon Jun 14 19:24:59 CST 2021, time=2021-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=895430, encodeId=6e9b8954308f, content=慢性炎症足以诱导产生人PAH的特征性血管病变和生理特征。该研究可为开辟治疗PAH的新途径提供线索。, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae205385871, createdName=Lexi, createdTime=Thu Oct 29 15:27:38 CST 2020, time=2020-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894743, encodeId=c9f0894e43e7, content=该研究在肺动脉高压的慢性炎症小鼠模型中全面分析了肺动脉逐步重构的特征。, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae205385871, createdName=Lexi, createdTime=Tue Oct 27 10:44:08 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050910, encodeId=dbc61050910e1, content=肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Mon Oct 26 20:24:59 CST 2020, time=2020-10-26, status=1, ipAttribution=)]
    2020-10-26 明天jing

    肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。

    0

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