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Circ Res：BMAL1下调通过增强氧化应激加重牙龈卟啉单胞菌引起的动脉粥样硬化

2020-02-22 不详 网络

关注

动脉粥样硬化性心血管疾病（ACVD）是全球死亡的主要原因。ACVD被认为是慢性炎症过程。除了与心血管系统本身相关的危险因素外，诸如牙周炎相关的牙龈卟啉单胞菌（P. gingivalis）等病原菌也与动脉粥样硬化的发展密切相关，但其潜在机制仍难以捉摸。本研究旨在阐明牙龈卟啉单胞菌促进动脉粥样硬化的机制，并探索新的ACVD治疗策略。建立Bmal1-/-小鼠，ApoE-/-小鼠，Bmal1-/-ApoE

动脉粥样硬化性心血管疾病（ACVD）是全球死亡的主要原因。ACVD被认为是慢性炎症过程。除了与心血管系统本身相关的危险因素外，诸如牙周炎相关的牙龈卟啉单胞菌（P. gingivalis）等病原菌也与动脉粥样硬化的发展密切相关，但其潜在机制仍难以捉摸。本研究旨在阐明牙龈卟啉单胞菌促进动脉粥样硬化的机制，并探索新的ACVD治疗策略。

建立Bmal1-/-小鼠，ApoE-/-小鼠，Bmal1-/-ApoE-/-小鼠，条件性内皮细胞Bmal1敲除小鼠（Bmal1fl / fl；Tek-Cre小鼠）和相应的有腿动物模型。牙龈卟啉单胞菌通过触发ApoE-/-小鼠的动脉氧化应激和炎症反应，并伴有昼夜节律紊乱，从而加速动脉粥样硬化的发展。昼夜节律紊乱促进了牙龈卟啉单胞菌引起的动脉粥样硬化进展。组织学结果显示，牙龈卟啉单胞菌感染激活TLRs-NF-κB信号转导轴，随后募集DNMT-1使BMAL1启动子甲基化，从而抑制BMAL1转录。BMAL1的下调释放了CLOCK，CLOCK磷酸化了p65，并进一步增强了NF-κB信号传导，从而提高了人主动脉内皮细胞的氧化应激和炎症反应。此外，小鼠模型显示甲硝唑和褪黑激素的联合给药是治疗ACVD的有效策略。

综上所述，该研究结果表明，牙龈卟啉单胞菌通过NF-κB-BMAL1-NF-κB信号传导通路促进动脉粥样硬化。褪黑激素和甲硝唑有望成为ACVD的辅助药物。

原始出处：

Xie M, Tang Q, et al., BMAL1-Downregulation Aggravates Porphyromonas Gingivalis-Induced Atherosclerosis by Encouraging Oxidative Stress. Circ Res. 2020 Feb 11. doi: 10.1161/CIRCRESAHA.119.315502.

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    2020-09-20 ms1292405679162969

    #Bmal1#

    0

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    2020-08-10 huangshifeng

    #粥样硬化#

    0

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    2020-02-24 3631173

    #牙龈卟啉单胞菌#

    0

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    2020-02-24 ms1260584454294838

    #应激#

    0

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    2020-02-23 飛歌

    学习了很有用不錯

    0