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Atherosclerosis-associated endothelial cell apoptosis by miRNA let7-b-mediated downregulation of HAS-2
Lijie Zhu1,2,3, Qingman Li1,2,3, Datun Qi1,2,3
1Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, Henan, PR China.
Abstract:
MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of human diseases including atherosclerosis. Increasing numbers of miRNAs have been identified to be important regulators in the progression of atherosclerosis by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in atherosclerosis need fully elucidation. In the present study, the function of miRNA let-7b was investigated in human aortic endothelial cells (HAECs). The results showed that downregulation of let-7b in the high-fat diet mice and HAECs was inversely correlated with the expression level of HAS-2. upregulation of let-7b significantly reduced apoptosis of HAECs. The results also revealed that HAS-2 was a target gene of let-7b and HAS-2 reduction reversed the antiapoptotic effect of let-7b through regulation of the P13K/Akt pathway. These results together suggest the potential of regulating the let-7b expression and endothelial apoptosis against development and progression of atherosclerosis.
Insights
MicroRNA let-7b protects against atherosclerosis by reducing endothelial cell apoptosis. Upregulating let-7b inhibits HAS-2 expression, a key factor in disease progression, via the PI3K/Akt pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are crucial in disease pathophysiology, including atherosclerosis.
- Their specific roles and mechanisms in atherosclerosis progression require further investigation.
Purpose of the Study:
- To investigate the function of miRNA let-7b in human aortic endothelial cells (HAECs).
- To elucidate the underlying mechanisms of let-7b in atherosclerosis.
Main Methods:
- Investigated let-7b function in HAECs and high-fat diet-induced atherosclerosis models.
- Analyzed the correlation between let-7b and HAS-2 expression.
- Examined the effect of let-7b on endothelial cell apoptosis.
- Identified HAS-2 as a let-7b target gene and its role in the PI3K/Akt pathway.
Main Results:
- Downregulation of let-7b was observed in high-fat diet mice and HAECs, inversely correlated with HAS-2 expression.
- Upregulation of let-7b significantly reduced HAEC apoptosis.
- HAS-2 was confirmed as a direct target of let-7b.
- HAS-2 reduction reversed the anti-apoptotic effects of let-7b via the PI3K/Akt pathway.
Conclusions:
- let-7b plays a protective role in atherosclerosis by inhibiting endothelial cell apoptosis.
- Targeting let-7b expression offers a potential therapeutic strategy against atherosclerosis development and progression.
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