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Effects of microRNA-292-5p on myocardial ischemia–reperfusion injury through the peroxisome proliferator-activated receptor-α/-γ signaling pathway

Gene Therapy volume 25, pages 234–248 (2018)Cite this article

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Abstract

Ischemia–reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes, such as free radical damage and cell apoptosis. This study aims to investigate whether microRNA-292-5p (miR-292-5p) protects against myocardial ischemia–reperfusion injury (IRI) via the peroxisome proliferator-activated receptor (PPAR)-α/-γ signaling pathway in myocardial IRI mice models. Mouse models of myocardial IRI were established. Adult male C57BL/6 mice were divided into different groups. The hemodynamic indexes, levels of related inflammatory factors and serum myocardial enzymes, and malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was applied to determine infarct size. TUNEL staining was used to detect cardiomyocyte apoptosis. RT-qPCR and western blotting were performed to measure the related gene expressions. Compared with the model group and the T0070907 + miR-292-5p inhibitor, the miR-292-5p inhibitor group exhibited decreased incidence and duration time of ventricular tachycardia and ventricular fibrillation, serum myocardial enzymes, TNF-α, IL-6, IL-1β, MDA, cardiomyocyte apoptosis, expressions of Bax and p53 in addition to increased SOD and GSH-Px activity, and increased expressions of Bcl-2, PPARα, PPARγ, PLIN5, AQP7, and PCK1. The T0070907 group exhibited opposite results compared to the miR-292-5p inhibitor group. The results indicate that miR-292-5p downregulation protects against myocardial IRI through activation of the PPAR-α/PPAR-γ signaling pathway.

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References

  1. Jacobshagen C, Maier LS. Pathophysiology of chronic myocardial ischemia. Herz. 2013;38:329–33.

    Article  CAS  Google Scholar 

  2. Heusch G. Myocardial ischemia: lack of coronary blood flow or myocardial oxygen supply/demand imbalance? Circ Res. 2016;119:194–6.

    Article  CAS  Google Scholar 

  3. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, et al. Adiponectin protects against myocardial ischemia–reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005;11:1096–103.

    Article  CAS  Google Scholar 

  4. Song CL, Liu B, Diao HY, Shi YF, Li YX, Zhang JC, et al. The protective effect of microRNA-320 on left ventricular remodeling after myocardial ischemia–reperfusion injury in the rat model. Int J Mol Sci. 2014;15:17442–56.

    Article  Google Scholar 

  5. Fauconnier J, Meli AC, Thireau J, Roberge S, Shan J, Sassi Y, et al. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia–reperfusion. Proc Natl Acad Sci USA. 2011;108:13258–63.

    Article  CAS  Google Scholar 

  6. Hausenloy DJ, Yellon DM. Myocardial ischemia–reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013;123:92–100.

    Article  CAS  Google Scholar 

  7. Olson EN. MicroRNAs as therapeutic targets and biomarkers of cardiovascular disease. Sci Transl Med. 2014;6:239ps233.

    Article  Google Scholar 

  8. Topkara VK, Mann DL. Role of microRNAs in cardiac remodeling and heart failure. Cardiovasc Drugs Ther. 2011;25:171–82.

    Article  CAS  Google Scholar 

  9. Fic P, Kowalczuk K, Grabarska A, Stepulak A. MicroRNA—a new diagnostic tool in coronary artery disease and myocardial infarction. Post Hig Med Dosw. 2014;68:410–8.

    Article  Google Scholar 

  10. Ye Y, Perez-Polo JR, Qian J, Birnbaum Y. The role of microRNA in modulating myocardial ischemia–reperfusion injury. Physiol Genom. 2011;43:534–42.

    Article  CAS  Google Scholar 

  11. Luningschror P, Stocker B, Kaltschmidt B, Kaltschmidt C. miR-290 cluster modulates pluripotency by repressing canonical NF-kappaB signaling. Stem Cells. 2012;30:655–64.

    Article  Google Scholar 

  12. Tao L, Bei Y, Zhou Y, Xiao J, Li X. Non-coding RNAs in cardiac regeneration. Oncotarget. 2015;6:42613–22.

    PubMed  PubMed Central  Google Scholar 

  13. Pitto L, Rizzo M, Simili M, Colligiani D, Evangelista M, Mercatanti A, et al. miR-290 acts as a physiological effector of senescence in mouse embryo fibroblasts. Physiol Genom. 2009;39:210–8.

    Article  CAS  Google Scholar 

  14. Weiss JB, Eisenhardt SU, Stark GB, Bode C, Moser M, Grundmann S. MicroRNAs in ischemia–reperfusion injury. Am J Cardiovasc Dis. 2012;2:237–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Ravingerova T, Carnicka S, Nemcekova M, Ledvenyiova V, Adameova A, Kelly T, et al. PPAR-alpha activation as a preconditioning-like intervention in rats in vivo confers myocardial protection against acute ischaemia–reperfusion injury: involvement of PI3K-Akt. Can J Physiol Pharmacol. 2012;90:1135–44.

    Article  CAS  Google Scholar 

  16. Balakumar P, Mahadevan N. Interplay between statins and PPARs in improving cardiovascular outcomes: a double-edged sword? Br J Pharmacol. 2012;165:373–9.

    Article  CAS  Google Scholar 

  17. Meng Z, Yu XH, Chen J, Li L, Li S. Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-gamma activation. Acta Pharmacol Sin. 2014;35:1247–56.

    Article  CAS  Google Scholar 

  18. Ibanez B, Heusch G, Ovize M, Van de Werf F. Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol. 2015;65:1454–71.

    Article  Google Scholar 

  19. Morrison A, Li J. PPAR-gamma and AMPK--advantageous targets for myocardial ischemia/reperfusion therapy. Biochem Pharmacol. 2011;82:195–200.

    Article  CAS  Google Scholar 

  20. Mezzaroma E, Toldo S, Farkas D, Seropian IM, Van Tassell BW, Salloum FN, et al. The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci USA. 2011;108:19725–30.

    Article  CAS  Google Scholar 

  21. Reel B, Guzeloglu M, Bagriyanik A, Atmaca S, Aykut K, Albayrak G, et al. The effects of PPAR-gamma agonist pioglitazone on renal ischemia/reperfusion injury in rats. J Surg Res. 2013;182:176–84.

    Article  CAS  Google Scholar 

  22. Collins T, Cybulsky MI. NF-kappaB: pivotal mediator or innocent bystander in atherogenesis? J Clin Invest. 2001;107:255–64.

    Article  CAS  Google Scholar 

  23. Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, et al. PPARgamma signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19:557–66.

    Article  CAS  Google Scholar 

  24. Lecarpentier Y, Claes V, Duthoit G, Hebert JL. Circadian rhythms, Wnt/beta-catenin pathway and PPAR alpha/gamma profiles in diseases with primary or secondary cardiac dysfunction. Front Physiol. 2014;5:429.

    Article  Google Scholar 

  25. Chen L, Yang G. PPARs integrate the mammalian clock and energy metabolism. PPAR Res. 2014;2014:653017.

    PubMed  PubMed Central  Google Scholar 

  26. Birnbaum Y, Long B, Qian J, Perez-Polo JR, Ye Y. Pioglitazone limits myocardial infarct size, activates Akt, and upregulates cPLA2 and COX-2 in a PPAR-gamma-independent manner. Basic Res Cardiol. 2011;106:431–46.

    Article  CAS  Google Scholar 

  27. Wayman NS, Ellis BL, Thiemermann C. Ligands of the peroxisome proliferator-activated receptor-PPAR-a reduce myocardial infarct size. Med Sci Monit. 2002;8:BR243–247.

    CAS  PubMed  Google Scholar 

  28. Sundararajan S GJL, Victor NA, et al. PPARγ ligands reduce inflammation and infarction size in transient focal ischemia[J]. Neuroscience. 2005;130:685–96.

    Article  Google Scholar 

  29. Duan SZ, Usher MG, Mortensen RM. Peroxisome proliferator-activated receptor-gamma-mediated effects in the vasculature. Circ Res. 2008;102:283–94.

    Article  CAS  Google Scholar 

  30. Son NH, Park TS, Yamashita H, Yokoyama M, Huggins LA, Okajima K, et al. Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice. J Clin Invest. 2007;117:2791–801.

    Article  CAS  Google Scholar 

  31. Velmurugan G, Venkatesh Babu DD, Ramasamy S. Prolonged monocrotophos intake induces cardiac oxidative stress and myocardial damage in rats. Toxicology. 2013;307:103–8.

    Article  CAS  Google Scholar 

  32. Kim T, Yang Q. Peroxisome proliferator-activated receptors regulate redox signaling in the cardiovascular system. World J Cardiol. 2013;5:164–74.

    Article  Google Scholar 

  33. Bloch O, Sughrue ME, Mills SA, Parsa AT. Signaling pathways in cranial chondrosarcoma: potential molecular targets for directed chemotherapy. J Clin Neurosci. 2011;18:881–5.

    Article  CAS  Google Scholar 

  34. Roy MJ, Vom A, Czabotar PE, Lessene G. Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven pathway. Br J Pharmacol. 2014;171:1973–87.

    Article  CAS  Google Scholar 

  35. Mason RR, Watt MJ. Unraveling the roles of PLIN5: linking cell biology to physiology. Trends Endocrinol Metab. 2015;26:144–52.

    Article  CAS  Google Scholar 

  36. Katano T, Ito Y, Ohta K, Yasujima T, Inoue K, Yuasa H. Competitive inhibition of AQP7-mediated glycerol transport by glycerol derivatives. Drug Metab Pharmacokinet. 2014;29:348–51.

    Article  CAS  Google Scholar 

  37. Li R, Yan G, Li Q, Sun H, Hu Y, Sun J, et al. MicroRNA-145 protects cardiomyocytes against hydrogen peroxide (H(2)O(2))-induced apoptosis through targeting the mitochondria apoptotic pathway. PLoS ONE. 2012;7:e44907.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by Yunnan Provincial Science and Technology Plan Project on Applied Basic Research (No. 2012FB088; No. 2017FF117 (-064)) and Yunnan Provincial Applied Basic Research Program—Basic Research Projects (No. 2014NS243). We would like show sincere appreciation to the reviewers for critical comments on this article.

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Author notes

  1. These authors contributed equally: Zhen-Dong Zhu, Ji-Yun Ye.

Authors and Affiliations

  1. Department of Cardiovascular Diseases, The Third People’s Hospital of Yunnan Province, The Second Affiliated Hospital of Dali University, 650011, Kunming, People’s Republic of China

    Zhen-Dong Zhu

  2. Pathogenic Organisms Department of Experimental Center, School of Basic Medical Sciences, Kunming Medical University, 650500, Kunming, People’s Republic of China

    Ji-Yun Ye

  3. Clinical Laboratory, The First People’s Hospital of Yunnan Province, 650032, Kunming, People’s Republic of China

    Hua Niu

  4. Department of Geriatrics, The First People’s Hospital of Yunnan Province, 650032, Kunming, People’s Republic of China

    Yu-Mei Ma & Xue-Mei Fu

  5. Clinical Medicine College, Dali University, 671003, Dali, People’s Republic of China

    Zhong-Hua Xia

  6. School of Pharmaceutical Sciences & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, 650500, Kunming, People’s Republic of China

    Xuan Zhang

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Correspondence to Zhen-Dong Zhu or Xuan Zhang.

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Zhu, ZD., Ye, JY., Niu, H. et al. Effects of microRNA-292-5p on myocardial ischemia–reperfusion injury through the peroxisome proliferator-activated receptor-α/-γ signaling pathway. Gene Ther 25, 234–248 (2018). https://doi.org/10.1038/s41434-018-0014-y

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