Down-regulation of OIP5-AS1 inhibits obesity-induced myocardial pyroptosis and miR-22/NLRP3 inflammasome axis

  • Impact factors: 3.2
  • Publication: Immunity Inflammation and Disease
  • Author:Qingxiong Yue, Yan Liu, Jun Ji, Tao Hu, Tong Lin, Shuang Yu, Shijun Li, Nan Wu
  • DOI citation-doi:10.1002/iid3.1066
  • Date:2023-10-27

Background Obesity can induce myocardial pyroptosis, but the exact mechanism is still unknown. A recent study reported the association of opa-interacting protein 5-antisense transcript 1 (OIP5-AS1), an evolutionarily conserved long noncoding RNA, with pyroptosis. Therefore, this study aimed to investigate the role of OIP5-AS1 in obesity-induced myocardial pyroptosis. Methods OIP5-AS1 was downregulated in H9c2 cells, followed by treatment with 400 μM palmitic acid (PA). Propidium iodide (PI) staining, lactic dehydrogenase (LDH) release assay, caspase-1 activity assay, IL-1β, and IL-18 activity assay were performed to detect pyroptotic phenotype. The interaction between OIP5-AS1 and microRNAs (miRNAs) was analyzed using RNA pull-down and luciferase assay. The effect of OIP5-AS1 knockdown in high-fat diet (HFD)-induced obesity rat on cardiac function, myocardial hypertrophy, fibrosis, and remodeling was evaluated. Results Fat deposition was observed in cardiomyocytes 24 h after PA treatment; moreover, PA-treated cardiomyocytes showed significant increase in the rate of pyroptotic cells, release of LDH, protein expressions of NLRP3 and cleaved caspase-1, and the activity of caspase-1, IL-1β, and IL-18 as well as OIP5-AS1 expression. These findings suggested that PA activated pyroptosis and induced OIP5-AS1 expression in cardiomyocytes. Moreover, OIP5-AS1 knockdown inhibited PA-induced pyroptosis. Mechanistically, OIP5-AS1 was found to specifically bind to miR-22 and to regulate NLRP3 inflammasome-mediated pyroptosis via miR-22. Furthermore, OIP5-AS1 knockdown ameliorated HFD-induced cardiac dysfunction, myocardial hypertrophy, fibrosis, remodeling, and pyroptosis. Conclusion Our results revealed that downregulation of OIP5-AS1 can inhibit obesity-induced myocardial pyroptosis via miR-22/NLRP3 inflammasome axis. This finding lays a foundation of gene therapy for heart disease targeting OIP5-AS1.

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