Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis

Journal of Lipid Research

Hong Yin¹  Jiayan Guo²  Qingyuan Meng²  Hanbing Mei²  Zhen Sheng²  Murielle M. Véniant³ 

[1] For correspondence: Hong Yin;Amgen Biopharmaceutical Research and Development (Shanghai) Co., Ltd., Shanghai, China;Department of Cardiometabolic Disorders, Amgen Research, Amgen Inc., Thousand Oaks, CA, USA;

关键词: micro-ribonucleic acid;    inflammation;    apoptosis;    familial hypercholesterolemia;    low density lipoprotein receptor;    animal model;   

DOI  :  

来源: DOAJ

【 摘 要 】

Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLRW483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs). miR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFα-induced protein 3 (TNFAIP3) gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analyzed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-κB and p38/MAPK signaling pathways.

【 授权许可】

Unknown