BMAL1 suppresses ROS-induced endothelial-to-mesenchymal transition and atherosclerosis plaque progression via BMP signaling

American Journal of Translational Research

Mengjiao Zhu¹  Hanfei Tang² 

[1] Department of Orthodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China;Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

关键词: Atherosclerosis;    endothelial-to-mesenchymal transition;    BMAL1;    plaque stability;    BMP signaling;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Circadian rhythm disruption is intimately linked to atherosclerosis, and endothelial-to-mesenchymal transition (EndMT) is a major feature of atherosclerosis progression and unstable plaques. However, the mechanisms underlying the roles of Brain and Muscle ARNT-Like Protein-1 (BMAL1), an essential clock transcription activator, in EndMT and plaque instability have not been characterized. In the present study, we found a positive relationship among BMAL1 expression loss, EndMT, and plaque vulnerability in human carotid plaques. Furthermore, loss- and gain-of-function studies in human aortic endothelial cells (HAECs) revealed that BMAL1 inhibited oxidized low-density lipoprotein (oxLDL)-induced intracellular reactive oxygen species (ROS) accumulation and subsequent EndMT. Mechanistically, BMAL1 deficiency aggravated EndMT through BMP-mediated signaling. Collectively, our study demonstrates the underlying mechanism for the central role of BMAL1 loss in atherosclerosis progression and plaque stability transition promoted by oxidative stress, which can be targeted therapeutically to prevent the occurrence and progression of atherosclerosis.

【 授权许可】

CC BY-NC