期刊
JOURNAL OF LIPID RESEARCH
卷 61, 期 12, 页码 1764-1775出版社
ELSEVIER
DOI: 10.1194/jlr.RA120001121
关键词
micro-ribonucleic acid; inflammation; apoptosis; familial hypercholesterolemia; low density lipoprotein receptor; animal model; endothelial cells; tumor necrosis factor alpha-induced protein 3
资金
- Amgen Inc.
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 TNF alpha -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-kappa B and p38/MAPK signaling pathways.
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