MicroRNA-30c-5p inhibits NLRP3 inflammasome-mediated endothelial cell pyroptosis through FOXO3 down-regulation in atherosclerosis

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.08.049· OSTI ID:23134236

Li, Peng; Zhong, Xiaoming; Li, Juan; Liu, Hongyang; Ma, Xiang; He, Ruili; Zhao, Yanzhuo ^[1]

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1. Department of Cardiology, Huaihe Hospital of Henan University (China)

Highlights: • Addition of miR-30c-5p inhibited ox-LDL-induced pyroptosis in HAECs. • NLRP3 inflammasome was associated with miR-30c-5p-mediated HEACs pyroptosis. • FOXO3 was a target of miR-30c-5p. • Silencing of FOXO3 attenuated anti-miR-30c-5p-mediated HAECs pyroptosis. Atherosclerosis is a chronic inflammatory disease involved in endothelial dysfunction. Pyroptosis is a pro-inflammatory form of cell death and plays pivotal roles in atherosclerosis. MicroRNAs (miRNAs) are implicated in atherosclerosis, however the mechanisms that underlie miR-30c-5p is required for endothelial cell pyroptosis remain elusive. In the present study, we probed the interaction of miR-30c-5p with forkhead box O3 (FOXO3) and investigated the effect of miR-30c-5p and FOXO3 on NLRP3 inflammasome and endothelial cell pyroptosis. Introduction of oxidized low density lipoprotein (ox-LDL) dose-dependently increased lactate dehydrogenase (LDH) release as well as pyroptosis in human aortic endothelial cells (HAECs). On the basis of ox-LDL treatment, we found the expression of miR-30c-5p was impaired and enrichment of miR-30c-5p protected HAECs from ox-LDL-induced pyroptosis. Moreover, addition of miR-30c-5p inhibited ox-LDL-activated NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which was associated with HEACs pyroptosis. Nevertheless, miR-30c-5p failed to show efficacy of Toll-like receptor (TLR) signaling of NLRP3 inflammasome activation. Intriguingly, FOXO3 was suggested to be targeted by miR-30c-5p and addition of miR-30c-5p blocked FOXO3 expression, whereas miR-30c-5p depletion showed opposite effects. Furthermore, silencing of FOXO3 inhibited NLRP3-mediated pyroptosis and reversed anti-miR-30c-5p-induced activation of NLRP3 inflammasome and pyroptosis in HEACs with ox-LDL treatment. Our finding suggested that miR-30c-5p might play essential role in NLRP3 inflammasome-modulated cell pyroptosis by targeting FOXO3 in HAECs, providing a novel therapeutic avenue for atherosclerosis treatment.

• OSTI ID: 23134236
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARTERIOSCLEROSIS
INFLAMMATION
LACTATE DEHYDROGENASE
LIPOPROTEINS
RECEPTORS