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LncRNA H19 Mitigates Oxidized Low-Density Lipoprotein Induced Pyroptosis via Caspase-1 in Raw 264.7 Cells

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Abstract

Atherosclerosis (AS) is mainly characterized by the activation of inflammatory cells and chronic inflammatory responses after cell injury. Pyroptosis is a form of programmed cell death (PCD) accompanied by the release of inflammatory factors. Many studies have shown that pyroptosis plays an important role in AS. Increasing evidence also indicates that long non-coding RNA H19 (lncRNA H19) involved in AS. However, whether the role of lncRNA H19 in AS is related to pyroptosis and the underlying mechanisms are largely unknown. In this study, we found that oxidized low-density lipoprotein (ox-LDL) induced pyroptosis and decreased the expression of lncRNA H19 in Raw 264.7 cells. Besides, silencing endogenous lncRNA H19 increased inflammatory responses and pyroptosis while exogenous overexpression of lncRNA H19 reversed this effect. Notably, we identified that the inhibitor of caspase-1 (XV-765) completely abrogated the silencing endogenous lncRNA H19 mediated pyroptosis. In addition, we found that lncRNA H19 inhibited ox-LDL-induced activation of nuclear factor-kappa B (NF-κB), mitochondrial dysfunction, and reduced the production of reactive oxygen species (ROS). Moreover, VX-765 impaired the silencing endogenous lncRNA H19 mediated pyroptosis. Overall, these findings indicated that lncRNA H19 may play an important role in pyroptosis and may serve as a potential therapeutic target for AS.

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AVAILABILITY OF DATA AND MATERIAL

The analyzed data and material used to support the findings of this study are available from the corresponding author on reasonable request.

References

  1. Raggi, P., J. Genest, J.T. Giles, et al. 2018. Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions. Atherosclerosis 276: 98–108.

    Article  CAS  Google Scholar 

  2. Grootaert, M.O.J., M. Moulis, L. Roth, et al. 2018. Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis. Cardiovascular Research 114: 622–634.

    Article  CAS  Google Scholar 

  3. Singh, R.B., S.A. Mengi, Y.J. Xu, et al. 2002. Pathogenesis of atherosclerosis: A multifactorial process. Experimental and Clinical Cardiology 7: 40–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Gordon, S., and F.O. Martinez. 2010. Alternative activation of macrophages: Mechanism and functions. Immunity 32: 593–604.

    Article  CAS  Google Scholar 

  5. Poznyak, A.V., N.G. Nikiforov, A.M. Markin, et al. 2021. Overview of Ox-LDL and its impact on cardiovascular health: Focus on atherosclerosis. Frontiers in Pharmacology 11: 613780.

    Article  Google Scholar 

  6. Fredman, G., J. Hellmann, J.D. Proto, et al. 2016. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. Nature Communications 7: 12859.

    Article  CAS  Google Scholar 

  7. Tawakol, A., Z.A. Fayad, R. Mogg, et al. 2013. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: Results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. Journal of the American College of Cardiology 62: 909–917.

    Article  CAS  Google Scholar 

  8. Ridker, P.M., B.M. Everett, T. Thuren, et al. 2017. CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine 377: 1119–1131.

    Article  CAS  Google Scholar 

  9. Yu, J., X. Cui, X. Zhang, et al. 2020. Advances in the occurrence of pyroptosis: A novel role in atherosclerosis. Current Pharmaceutical Biotechnology. (Online ahead of print).

  10. Reisetter, A.C., L.V. Stebounova, J. Baltrusaitis, et al. 2011. Induction of inflammasome-dependent pyroptosis by carbon black nanoparticles. Journal of Biological Chemistry 286: 21844–21852.

    Article  CAS  Google Scholar 

  11. Xu, Y.J., L. Zheng, Y.W. Hu, et al. 2018. Pyroptosis and its relationship to atherosclerosis. Clinica Chimica Acta 476: 28–37.

    Article  CAS  Google Scholar 

  12. Shi, J., W. Gao, and F. Shao. 2017. Pyroptosis: Gasdermin-mediated programmed necrotic cell death. Trends in Biochemical Sciences 42: 245–254.

    Article  CAS  Google Scholar 

  13. Duewell, P., H. Kono, K.J. Rayner, et al. 2010. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464: 1357–1361.

    Article  CAS  Google Scholar 

  14. Afrasyab, A., P. Qu, Y. Zhao, et al. 2016. Correlation of NLRP3 with severity and prognosis of coronary atherosclerosis in acute coronary syndrome patients. Heart and Vessels 31: 1218–1229.

    Article  Google Scholar 

  15. Peng, X., H. Chen, Y. Li, et al. 2020. Effects of NIX-mediated mitophagy on ox-LDL-induced macrophage pyroptosis in atherosclerosis. Cell Biology International 44: 1481–1490.

    Article  CAS  Google Scholar 

  16. Zhang, Y., X. Liu, X. Bai, et al. 2018. Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR-223/NLRP3 axis. Journal of Pineal Research 64.

  17. Li, X., L. Zeng, C. Cao, et al. 2017. Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy. Experimental Cell Research 350: 327–335.

    Article  CAS  Google Scholar 

  18. Li, J., C. Yang, Y. Li, et al. 2018. LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation. Bioscience Reports 38: BSR20171150.

  19. Shi, X., Y.T. Wei, H. Li, et al. 2020. Long non-coding RNA H19 in atherosclerosis: What role? Molecular Medicine 26: 72.

    Article  Google Scholar 

  20. Sun, H., Q. Jiang, L. Sheng, et al. 2020. Downregulation of lncRNA H19 alleviates atherosclerosis through inducing the apoptosis of vascular smooth muscle cells. Molecular Medicine Reports 22: 3095–3102.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Yang, Y., F. Tang, F. Wei, et al. 2019. Silencing of long non-coding RNA H19 downregulates CTCF to protect against atherosclerosis by upregulating PKD1 expression in ApoE knockout mice. Aging (Albany NY) 11: 10016–10030.

    Article  CAS  Google Scholar 

  22. Wang, Y., and I. Tabas. 2014. Emerging roles of mitochondria ROS in atherosclerotic lesions: Causation or association? Journal of Atherosclerosis and Thrombosis 21: 381–390.

    Article  Google Scholar 

  23. Zhaolin, Z., C. Jiaojiao, W. Peng, et al. 2019. Ox-LDL induces vascular endothelial cell pyroptosis through miR-125a-5p/TET2 pathway. Journal of Cellular Physiology 234: 7475–7491.

    Article  Google Scholar 

  24. Sheedy, F.J., A. Grebe, K.J. Rayner, et al. 2013. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nature Immunology 14: 812–820.

    Article  CAS  Google Scholar 

  25. Doitsh, G., N.L. Galloway, X. Geng, et al. 2014. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505: 509–514.

    Article  CAS  Google Scholar 

  26. Broz, P. 2015. Immunology: Caspase target drives pyroptosis. Nature 526: 642–643.

    Article  CAS  Google Scholar 

  27. Zheng, F., Z. Gong, S. Xing, et al. 2014. Overexpression of caspase-1 in aorta of patients with coronary atherosclerosis. Heart, Lung & Circulation 23: 1070–1074.

    Article  Google Scholar 

  28. Gage, J., M. Hasu, M. Thabet, et al. 2012. Caspase-1 deficiency decreases atherosclerosis in apolipoprotein E-null mice. Canadian Journal of Cardiology 28: 222–229.

    Article  CAS  Google Scholar 

  29. Li, Y.Y., S.H. Zhou, S.S. Chen, et al. 2020. PRMT2 inhibits the formation of foam cell induced by ox-LDL in RAW 264.7 macrophage involving ABCA1 mediated cholesterol efflux. Biochemical and Biophysical Research Communications 524: 77–82.

    Article  CAS  Google Scholar 

  30. Yu, X.H., Y.C. Fu, D.W. Zhang, et al. 2013. Foam cells in atherosclerosis. Clinica Chimica Acta 424: 245–252.

    Article  CAS  Google Scholar 

  31. Janabi, M., S. Yamashita, K. Hirano, et al. 2000. Oxidized LDL-induced NF-kappa B activation and subsequent expression of proinflammatory genes are defective in monocyte-derived macrophages from CD36-deficient patients. Arteriosclerosis, Thrombosis, and Vascular Biology 20: 1953–1960.

    Article  CAS  Google Scholar 

  32. Lin, S.J., H.T. Yen, Y.H. Chen, et al. 2003. Expression of interleukin-1 beta and interleukin-1 receptor antagonist in ox-LDL-treated human aortic smooth muscle cells and in the neointima of cholesterol-fed endothelia-denuded rabbits. Journal of Cellular Biochemistry 88: 836–847.

    Article  CAS  Google Scholar 

  33. Jiang, Y., K. Huang, X. Lin, et al. 2017. Berberine attenuates NLRP3 inflammasome activation in macrophages to reduce the secretion of interleukin-1β. Annals of Clinical and Laboratory Science 47: 720–728.

    CAS  PubMed  Google Scholar 

  34. Li, X., H. Wang, B. Yao, et al. 2016. lncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy. Science and Reports 6: 36340.

    Article  CAS  Google Scholar 

  35. Zhang, X., S. Ji, G. Cai, et al. 2020. H19 Increases IL-17A/IL-23 releases via regulating VDR by interacting with miR675-5p/miR22-5p in ankylosing spondylitis. Molecular Therapy-Nucleic Acids 19: 393–404.

    Article  CAS  Google Scholar 

  36. Sen, R., and D. Baltimore. 1986. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 47: 921–928.

    Article  CAS  Google Scholar 

  37. Pamukcu, B., G.Y. Lip, and E. Shantsila. 2011. The nuclear factor-kappa B pathway in atherosclerosis: A potential therapeutic target for atherothrombotic vascular disease. Thrombosis Research 128: 117–123.

    Article  CAS  Google Scholar 

  38. Lima, G.F., R.O. Lopes, A.B.A. Mendes, et al. 2020. Inosine, an endogenous purine nucleoside, avoids early stages of atherosclerosis development associated to eNOS activation and p38 MAPK/NF-kB inhibition in rats. European Journal of Pharmacology 882: 173289.

    Article  CAS  Google Scholar 

  39. Qin, M., Y. Luo, S. Lu, et al. 2017. Ginsenoside F1 ameliorates endothelial cell inflammatory injury and prevents atherosclerosis in mice through a20-mediated suppression of NF-kB signaling. Frontiers in Pharmacology 8: 953.

    Article  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (grant number 81773934) and Graduate Innovation Fund of Jilin University (grant number 101832020CX319).

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Authors and Affiliations

  1. Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, 130021, China

    Shan Liu, Jiu-long Ma, Peng Huang, Di Wu & Li-qun Ren

  2. Cancer Center, the First Hospital of Jilin University, Changchun, Jilin, 130021, China

    Dong-sheng Xu

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  1. Shan Liu
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  2. Dong-sheng Xu
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  3. Jiu-long Ma
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  4. Peng Huang
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Contributions

SL designed and performed the experiments and wrote the manuscript; LR revised the manuscript. DX, JM, PH, and DW contributed to experimental work and data analysis. All authors have read and approved the final version of the manuscript.

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Correspondence to Li-qun Ren.

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Liu, S., Xu, Ds., Ma, Jl. et al. LncRNA H19 Mitigates Oxidized Low-Density Lipoprotein Induced Pyroptosis via Caspase-1 in Raw 264.7 Cells. Inflammation 44, 2407–2418 (2021). https://doi.org/10.1007/s10753-021-01511-1

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  • DOI: https://doi.org/10.1007/s10753-021-01511-1

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