Journal
CELL DEATH & DISEASE
Volume 12, Issue 4, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-021-03671-2
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Funding
- National Natural Science Foundation of China [81970198, 81770473]
- Taishan Scholar Project of Shandong Province of China [tsqn20161066]
- Natural Science Foundation for Distinguished Young Scholars of Shandong Province [ZR2020JQ30]
- Natural Science Foundation of Shandong Province [ZR2020MH132]
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HuR plays a crucial protective role against atherosclerosis by increasing AMPK-mediated autophagy to reduce plaque formation.
Human antigen R (HuR) is a widespread RNA-binding protein involved in homeostatic regulation and pathological processes in many diseases. Atherosclerosis is the leading cause of cardiovascular disease and acute cardiovascular events. However, the role of HuR in atherosclerosis remains unknown. In this study, mice with smooth muscle-specific HuR knockout (HuR(SMKO)) were generated to investigate the role of HuR in atherosclerosis. HuR expression was reduced in atherosclerotic plaques. As compared with controls, HuR(SMKO) mice showed increased plaque burden in the atherosclerotic model. Mechanically, HuR could bind to the mRNAs of adenosine 5 '-monophosphate-activated protein kinase (AMPK) alpha 1 and AMPK alpha 2, thus increasing their stability and translation. HuR deficiency reduced p-AMPK and LC3II levels and increased p62 level, thereby resulting in defective autophagy. Finally, pharmacological AMPK activation induced autophagy and suppressed atherosclerosis in HuR(SMKO) mice. Our findings suggest that smooth muscle HuR has a protective effect against atherosclerosis by increasing AMPK-mediated autophagy.
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