文章基本信息

标题：Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis
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作者：Jiayan Guo ; Hanbing Mei ; Zhen Sheng 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2020
卷号：61
期号：12
页码：1764-1775
DOI：10.1194/jlr.RA120001121
出版社：American Society for Biochemistry and Molecular Biology
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 LDLR W483X 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.
关键词：micro-ribonucleic acid ; inflammation ; apoptosis ; familial hypercholesterolemia ; low density lipoprotein receptor ; animal model ; endothelial cells ; tumor necrosis factor α-induced protein 3