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Clock Gene Bmal1 Disruption in Vascular Smooth Muscle Cells Worsens Carotid Atherosclerotic Lesions 期刊论文

编号：

2E015E97A040C6145029C3B4A25ED1E0
作者：

Lin, Changpo(林长泼)#^[1,2,3,5]Xu, Lirong^[1];Tang, Xiao^[2,3];Li, Xiaobo^[4,5];Lu, Chao;Cheng, Qianyun^[5];Jiang, Junhao(蒋俊豪)^[1,2,3]Shen, Yang^[1,2,3];Yan, Dong(严栋)^[1,2,3]Qian, Ruizhe^[5];Fu, Weiguo(符伟国)*^[1,2,3]Guo, Daqiao(郭大乔)*^[1,2,3]
语种：

英文
期刊：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY ISSN：1079-5642 2022 年 42 卷 5 期 (565 - 579) ; MAY
收录：
关键词：

apoptosis atherosclerosis cardiovascular diseases cell migration circadian clocks reactive oxygen species smooth muscle cells
摘要：

Background: Clock system disruptions are associated with cardiovascular diseases. We previously demonstrated Bmal1 (brain muscle aryl nuclear translocase like-1) expression is significantly attenuated in plaque-derived vascular smooth muscle cells (VSMCs). However, the influence of Bmal1 disruption in VSMCs and its molecular targets are still unclear. Here, we aim to define how Bmal1 disruption in VSMCs influences the atherosclerosis lesions. Methods: The relationship among Bmal1, neurological symptoms, and plaque stability was investigated. VSMC Bmal1(-/-) and VSMC Bmal1(+/+)mice were generated and injected with adeno associated virus encoding mutant proprotein convertase subtilisin/kexin type 9 to induce atherosclerosis. Carotid artery ligation and cuff placement were performed in these mice to confirm the role of Bmal1 in atherosclerosis progression. The relevant molecular mechanisms were then explored. Results: Bmal1 expression in the carotid plague was significantly lower in symptomatic patients as well as in unstable plaques. Moreover, Bmal1 reduction is an independent risk factor for neurological symptoms and plaque instability. Besides, VSMC Bmal1(-/-) mice exhibit aggravated atherosclerotic lesions. Further study demonstrated that Bmal1 downregulation in VSMCs increased VSMC migration, monocyte transmigration, reactive oxygen species levels, and VSMCs apoptosis. As for the mechanism, we revealed that Bmal1 suppresses VSMCs migration by inhibiting RAC1 activity in 2 ways: by activating the transcription of RhoGDI alpha and by interacting with RAC1. Besides, Bmal1 was shown to preserve antioxidant function in VSMCs by activating Nrf2 (nuclear factor erythroid 2-related factor 2) and Bcl-2 transcription. Conclusions: Bmal1 disruption in VSMCs worsens atherosclerosis by promoting VSMC migration and monocyte transmigration and impairing antioxidant function. Therefore, Bmal1 may be a potential therapeutic target and biomarker of atherosclerosis in the future.
推荐引用方式
GB/T 7714：

Lin Changpo,Xu Lirong,Tang Xiao, et al. Clock Gene Bmal1 Disruption in Vascular Smooth Muscle Cells Worsens Carotid Atherosclerotic Lesions [J].ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2022,42(5):565-579.
APA：

Lin Changpo,Xu Lirong,Tang Xiao,Li Xiaobo,&Guo Daqiao.(2022).Clock Gene Bmal1 Disruption in Vascular Smooth Muscle Cells Worsens Carotid Atherosclerotic Lesions .ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,42(5):565-579.
MLA：

Lin Changpo, et al. "Clock Gene Bmal1 Disruption in Vascular Smooth Muscle Cells Worsens Carotid Atherosclerotic Lesions" .ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 42,5(2022):565-579.
入库时间：

2023/12/2 0:00:00
更新时间：

2023/12/2 0:00:00

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