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Regulation of autophagy of the heart in ischemia and reperfusion

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Abstract

Ischemia/reperfusion (I/R) of the heart leads to increased autophagic flux. Preconditioning stimulates autophagic flux by AMPK and PI3-kinase activation and mTOR inhibition. The cardioprotective effect of postconditioning is associated with activation of autophagy and increased activity of NO-synthase and AMPK. Oxidative stress stimulates autophagy in the heart during I/R. Superoxide radicals generated by NADPH-oxidase acts as a trigger for autophagy, possibly due to AMPK activation. There is reason to believe that AMPK, GSK-3β, PINK1, JNK, hexokinase II, MEK, PKCα, and ERK kinases stimulate autophagy, while mTOR, PKCδ, Akt, and PI3-kinase can inhibit autophagy in the heart during I/R. However, there is evidence that PI3-kinase could stimulate autophagy in ischemic preconditioning of the heart. It was found that transcription factors FoxO1, FoxO3, NF-κB, HIF-1α, TFEB, and Nrf-2 enhance autophagy in the heart in I/R. Transcriptional factors STAT1, STAT3, and p53 inhibit autophagy in I/R. MicroRNAs could stimulate and inhibit autophagy in the heart in I/R. Long noncoding RNAs regulate the viability and autophagy of cardiomyocytes in hypoxia/reoxygenation (H/R). Nitric oxide (NO) donors and endogenous NO could activate autophagy of cardiomyocytes. Activation of heme oxygenase-1 promotes cardiomyocyte tolerance to H/R and enhances autophagy. Hydrogen sulfide increases cardiac tolerance to I/R and inhibits apoptosis and autophagy via mTOR and PI3-kinase activation.

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Data Availability

The datasets analysed during the current study are available in the PubMed repository.

References

  1. van der Ende MY, Juarez-Orozco LE, Waardenburg I et al (2020) Sex-based differences in unrecognized myocardial infarction. J Am Heart Assoc 9(13):e015519. https://doi.org/10.1161/JAHA.119.015519

    Article  PubMed  PubMed Central  Google Scholar 

  2. Geyer S, Eberhard S, Schmidt BMW et al (2018) Morbidity compression in myocardial infarction 2006 to 2015 in terms of changing rates and age at occurrence: a longitudinal study using claims data from Germany. PLoS ONE 13(8):e0202631. https://doi.org/10.1371/journal.pone.0202631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dalen JE, Alpert JS, Goldberg RJ, Weinstein RS (2014) The epidemic of the 20(th) century: coronary heart disease. Am J Med 127(9):807–812. https://doi.org/10.1016/j.amjmed.2014.04.015

    Article  PubMed  Google Scholar 

  4. Menees DS, Peterson ED, Wang Y et al (2013) Door-to-balloon time and mortality among patients undergoing primary PCI. N Engl J Med 369(10):901–909. https://doi.org/10.1056/NEJMoa1208200

    Article  CAS  PubMed  Google Scholar 

  5. Fabris E, Kilic S, Schellings DAAM et al (2017) Long-term mortality and prehospital tirofiban treatment in patients with ST elevation myocardial infarction. Heart 103(19):1515–1520. https://doi.org/10.1136/heartjnl-2017-311181

    Article  CAS  PubMed  Google Scholar 

  6. Vaidya SR, Devarapally SR, Arora S (2017) Infarct related artery only versus complete revascularization in ST-segment elevation myocardial infarction and multi vessel disease: a meta-analysis. Cardiovasc Diagn Ther 7(1):16–26. https://doi.org/10.21037/cdt.2016.08.06

    Article  PubMed  PubMed Central  Google Scholar 

  7. Olier I, Sirker A, Hildick-Smith DJR (2018) British Cardiovascular Intervention Society and the National Institute for Cardiovascular Outcomes Research. Association of different antiplatelet therapies with mortality after primary percutaneous coronary intervention. Heart 104(20):1683–1690. https://doi.org/10.1136/heartjnl-2017-312366

    Article  CAS  PubMed  Google Scholar 

  8. Bessonov IS, Kuznetsov VA, Gorbatenko EA et al (2021) Influence of total ischemic time on clinical outcomes in patients with ST-segment elevation myocardial infarction. Kardiologiia 61(2):40–46. https://doi.org/10.18087/cardio.2021.2.n1314

    Article  CAS  PubMed  Google Scholar 

  9. Megaly M, Pershad A, Glogoza M et al (2021) Use of intravascular imaging in patients with ST-segment elevation acute myocardial infarction. Cardiovasc Revasc Med 30:59–64. https://doi.org/10.1016/j.carrev.2020.09.032

    Article  PubMed  Google Scholar 

  10. McCartney PJ, Berry C (2019) Redefining successful primary PCI. Eur Heart J Cardiovasc Imaging 20(2):133–135. https://doi.org/10.1093/ehjci/jey159

    Article  PubMed  Google Scholar 

  11. Basir MB, Lemor A, Gorgis S et al (2022) National Cardiogenic Shock Initiative Investigators. Vasopressors independently associated with mortality in acute myocardial infarction and cardiogenic shock. Catheter Cardiovasc Interv 99(3):650–657. https://doi.org/10.1002/ccd.29895

    Article  PubMed  Google Scholar 

  12. de Duve C, Pressman BC, Gianetto R et al (1955) Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J 60(4):604–617. https://doi.org/10.1042/bj0600604

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bainton DF (1981) The discovery of lysosomes. J Cell Biol 91(3):66s–676. https://doi.org/10.1083/jcb.91.3.66s

    Article  CAS  PubMed  Google Scholar 

  14. de Duve C (1983) Lysosomes revisited. Eur J Biochem 137(3):391–397. https://doi.org/10.1111/j.1432-1033.1983.tb07841.x

    Article  PubMed  Google Scholar 

  15. Ashford TP, Porter KR (1962) Cytoplasmic components in hepatic cell lysosomes. J Cell Biol 12(1):198–202. https://doi.org/10.1083/jcb.12.1.198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Klionsky DJ (2008) Autophagy revisited: a conversation with Christian de Duve. Autophagy 4(6):740–743. https://doi.org/10.4161/auto.6398

    Article  PubMed  Google Scholar 

  17. Radewa J (1963) Observations on autophagocytosis phenomena in the blood. Z Rheumaforsch 22:36–46

    CAS  PubMed  Google Scholar 

  18. Deter RL, Baudhuin P, de Duve C (1967) Participation of lysosomes in cellular autophagy induced in rat liver by glucagon. J Cell Biol 35(2):11–16. https://doi.org/10.1083/jcb.35.2.c11

    Article  Google Scholar 

  19. Deter RL, de Duve C (1967) Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. J Cell Biol 33(2):437–449. https://doi.org/10.1083/jcb.33.2.437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sciarretta S, Maejima Y, Zablocki D et al (2018) The role of autophagy in the heart. Annu Rev Physiol 80(1):1–26. https://doi.org/10.1146/annurev-physiol-021317-121427

    Article  CAS  PubMed  Google Scholar 

  21. Shintani T, Klionsky DJ, Shintani T et al (2004) Autophagy in health and disease: a double-edged sword. Science 306(5698):990–995. https://doi.org/10.1126/science.1099993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ravikumar B, Sarkar S, Davies JE et al (2010) Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 90(4):1383–1435. https://doi.org/10.1152/physrev.00030.2009

    Article  CAS  PubMed  Google Scholar 

  23. Singh KK, Yanagawa B, Quan A et al (2014) Autophagy gene fingerprint in human ischemia and reperfusion. J Thorac Cardiovasc Surg 147(3):1065–1072. https://doi.org/10.1016/j.jtcvs.2013.04.042

    Article  CAS  PubMed  Google Scholar 

  24. Huang C, Andres AM, Ratliff EP et al (2011) Preconditioning involves selective mitophagy mediated by Parkin and p62/SQSTM1. PLoS ONE 6(6):e20975. https://doi.org/10.1371/journal

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Klionsky DJ, Abdel-Aziz AK, Sara Abdelfatah S et al (2021) Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy 17(1):1-382. https://doi.org/10.1080/15548627.2020.1797280

  26. Vélez DE, Hermann R, Frank MB et al (2016) Effects of wortmannin on cardioprotection exerted by ischemic preconditioning in rat hearts subjected to ischemia-reperfusion. J Physiol Biochem 72(1):83–91. https://doi.org/10.1007/s13105-015-0460-6

    Article  CAS  PubMed  Google Scholar 

  27. García-Rúa V, Feijóo-Bandín S, Rodríguez-Penas D et al (2016) Endolysosomal two-pore channels regulate autophagy in cardiomyocytes. J Physiol 594(11):3061–3077. https://doi.org/10.1113/JP271332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang A, Zhang H, Liang Z et al (2016) U0126 attenuates ischemia/reperfusion-induced apoptosis and autophagy in myocardium through MEK/ERK/EGR-1 pathway. Eur J Pharmacol 88:280–285. https://doi.org/10.1016/j.ejphar.2016.06.038

    Article  CAS  Google Scholar 

  29. Hua P, Liu J, Tao J et al (2017) Efficacy and mechanism of preoperative simvastatin therapy on myocardial protection after extracorporeal circulation. Biomed Res Int 2017:6082430. https://doi.org/10.1155/2017/6082430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tang H, Song X, Ling Y et al (2017) Puerarin attenuates myocardial hypoxia/reoxygenation injury by inhibiting autophagy via the Akt signaling pathway. Mol Med Rep 5(6):3747–3754. https://doi.org/10.3892/mmr.2017.6424

    Article  CAS  Google Scholar 

  31. Ye G, Fu Q, Jiang L et al (2018) Vascular smooth muscle cells activate PI3K/Akt pathway to attenuate myocardial ischemia/reperfusion-induced apoptosis and autophagy by secreting bFGF. Biomed Pharmacother 107:1779–1785. https://doi.org/10.1016/j.biopha.2018.05.113

    Article  CAS  PubMed  Google Scholar 

  32. Su Q, Liu Y, Lv X-W et al (2019) Inhibition of lncRNA TUG1 upregulates miR-142-3p to ameliorate myocardial injury during ischemia and reperfusion via targeting HMGB1- and Rac1-induced autophagy. J Mol Cell Cardiol 133:12–25. https://doi.org/10.1016/j.yjmcc.2019.05.021

    Article  CAS  PubMed  Google Scholar 

  33. Shao J, Miao C, Geng Z et al (2019) Effect of eNOS on ischemic postconditioning-induced autophagy against ischemia/reperfusion injury in mice. Biomed Res Int 2019(6):10155–10163. https://doi.org/10.1155/2019/5201014

    Article  CAS  Google Scholar 

  34. Wang Y, Yang Z, Zheng G et al (2019) Metformin promotes autophagy in ischemia/reperfusion myocardium via cytoplasmic AMPKα1 and nuclear AMPKα2 pathways. Life Sci 225:64–71. https://doi.org/10.1016/j.lfs.2019.04.002

    Article  CAS  PubMed  Google Scholar 

  35. Zhong Y, Zhong P, He S et al (2017) Trimetazidine protects cardiomyocytes against hypoxia/reoxygenation injury by promoting AMP-activated protein kinase–dependent autophagic Flux. J Cardiovasc Pharmacol 69(6):389–397. https://doi.org/10.1097/FJC.0000000000000487

    Article  CAS  PubMed  Google Scholar 

  36. Jahania SM, Sengstock D, Vaitkevicius P et al (2013) Activation of the homeostatic intracellular repair response during cardiac surgery. J Am Coll Surg 216(4):719–726. https://doi.org/10.1016/j.jamcollsurg.2012.12.034

    Article  PubMed  PubMed Central  Google Scholar 

  37. Marek-Iannucci S, Thomas A, Hou J et al (2019) Myocardial hypothermia increases autophagic flux, mitochondrial mass and myocardial function after ischemia-reperfusion injury. Sci Rep 9(1):10001. https://doi.org/10.1038/s41598-019-46452-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhao T, Huang X, Han L et al (2012) Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes. J Biol Chem 287(28):23615–23625. https://doi.org/10.1074/jbc.M112.379164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gottlieb RA, Andres AM, Sin J et al (2015) Untangling autophagy measurements. Circ Res 116(3):504–514. https://doi.org/10.1161/CIRCRESAHA.116.303787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Decker RS, Wildenthal K (1980) Lysosomal alterations in hypoxic and reoxygenated hearts. I. Ultrastructural and cytochemical changes. Am J Pathol 98(2):425–444

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Yan L, Vatner DE, Kim S-J et al (2005) Autophagy in chronically ischemic myocardium. Proc Natl Acad Sci USA 102(39):13807–13812. https://doi.org/10.1073/pnas.0506843102

    Article  PubMed  PubMed Central  Google Scholar 

  42. Valentim L, Laurence KM, Townsend PA et al (2006) Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury. J Mol Cell Cardiol 40(6):846–852. https://doi.org/10.1016/j.yjmcc.2006.03.428

    Article  CAS  PubMed  Google Scholar 

  43. De Meyer GRY, Martinet W (2009) Autophagy in the cardiovascular system. Biochim Biophys Acta Mol Cell Res 1793(9):1485–1495. https://doi.org/10.1016/j.bbamcr.2008.12.01

    Article  Google Scholar 

  44. Qian J, Ren X, Wang X et al (2009) Blockade of Hsp20 phosphorylation exacerbates cardiac ischemia/reperfusion injury by suppressed autophagy and increased cell death. Circ Res 105(12):1223–1231. https://doi.org/10.1161/CIRCRESAHA.109.200378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kanamori H, Takemura G, Goto K et al (2011) Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion. Am J Physiol Circ Physiol 300(6):H2261–H2271. https://doi.org/10.1152/ajpheart.01056.2010

    Article  CAS  Google Scholar 

  46. Sciarretta S, Hariharan N, Monden Y et al (2011) Is autophagy in response to ischemia and reperfusion protective or detrimental for the heart? Pediatr Cardiol 32(3):275–281. https://doi.org/10.1007/s00246-010-9855-x

    Article  PubMed  Google Scholar 

  47. Sengupta A, Molkentin JD, Paik J-H et al (2011) FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress. J Biol Chem 286(9):7468–7478. https://doi.org/10.1074/jbc.M110.179242

    Article  CAS  PubMed  Google Scholar 

  48. Yan L, Sadoshima J, Vatner DE et al (2009) Autophagy in ischemic preconditioning and hibernating myocardium. Autophagy 5(5):709–712. https://doi.org/10.4161/auto.5.5.8510

    Article  CAS  PubMed  Google Scholar 

  49. Sala-Mercado JA, Wider J, Reddy Undyala VV et al (2010) Profound Cardioprotection With Chloramphenicol Succinate in the Swine Model of Myocardial Ischemia-Reperfusion Injury. Circulation 122:S179–S184. https://doi.org/10.1161/CIRCULATIONAHA.109.928242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ma X, Liu H, Foyil SR et al (2012) Impaired Autophagosome Clearance Contributes to Cardiomyocyte Death in Ischemia/Reperfusion Injury. Circulation 125(25):3170–3181. https://doi.org/10.1161/CIRCULATIONAHA.111.041814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ma M-Q, Thapalia BA, Lin X-H (2015) A 6 hour therapeutic window, optimal for interventions targeting AMPK synergism and apoptosis antagonism, for cardioprotection against myocardial ischemic injury: an experimental study on rats. Am J Cardiovasc Dis 5(1):63–71

    PubMed  PubMed Central  Google Scholar 

  52. Zhang H, Yin Y, Liu Y et al (2020) Necroptosis mediated by impaired autophagy flux contributes to adverse ventricular remodeling after myocardial infarction. Biochem Pharmacol 175:113915. https://doi.org/10.1016/j.bcp.2020.113915

    Article  CAS  PubMed  Google Scholar 

  53. Zhang Y, Yao Y, Fang N et al (2014) Restoration of autophagic flux in myocardial tissues is required for cardioprotection of sevoflurane postconditioning in rats. Acta Pharmacol Sin 35(6):758–769. https://doi.org/10.1038/aps.2014.20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wang Z-G, Wang Y, Huang Y et al (2015) bFGF regulates autophagy and ubiquitinated protein accumulation induced by myocardial ischemia/reperfusion via the activation of the PI3K/Akt/mTOR pathway. Sci Rep 5(1):9287. https://doi.org/10.1038/srep09287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Huang Z, Han Z, Ye B et al (2015) Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes. Eur J Pharmacol 762:1–10. https://doi.org/10.1016/j.ejphar.2015.05.028

    Article  CAS  PubMed  Google Scholar 

  56. Yu P, Zhang J, Yu S et al (2015) Protective Effect of Sevoflurane Postconditioning against Cardiac Ischemia/Reperfusion Injury via Ameliorating Mitochondrial Impairment, Oxidative Stress and Rescuing Autophagic Clearance. PLoS ONE 10(8):e0134666. https://doi.org/10.1371/j ournal.pone.0134666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Xuan F, Jian J, Lin X et al (2017) 17-Methoxyl-7-Hydroxy-Benzene-Furanchalcone Ameliorates Myocardial Ischemia/Reperfusion Injury in Rat by Inhibiting Apoptosis and Autophagy Via the PI3K–Akt Signal Pathway. Cardiovasc Toxicol 17(1):79–87. https://doi.org/10.1007/s12012-016-9358-y

    Article  CAS  PubMed  Google Scholar 

  58. Guo L, Xu J-M, Mo X-Y (2015) Ischemic postconditioning regulates cardiomyocyte autophagic activity following ischemia/reperfusion injury. Mol Med Rep 12(1):1169–1176. https://doi.org/10.3892/mmr.2015.3533

    Article  CAS  PubMed  Google Scholar 

  59. Wu X, He L, Chen F et al (2014) Impaired autophagy contributes to adverse cardiac remodeling in acute myocardial infarction. PLoS ONE 9(11):112891. https://doi.org/10.1371/journal.pone.0112891

    Article  CAS  Google Scholar 

  60. Zhao M, Sun L, Yu X-J et al (2013) Acetylcholine mediates AMPK-dependent autophagic cytoprotection in H9c2 cells during hypoxia/reoxygenation injury. Cell Physiol Biochem 32(3):601–613. https://doi.org/10.1159/000354464

    Article  CAS  PubMed  Google Scholar 

  61. Xu Q, Li X, Lu Y et al (2015) Pharmacological modulation of autophagy to protect cardiomyocytes according to the time windows of ischaemia/reperfusion. Br J Pharmacol 172(12):3072–3085. https://doi.org/10.1111/bph.13111v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Yang Y, Li Y, Chen X et al (2016) Exosomal transfer of miR-30a between cardiomyocytes regulates autophagy after hypoxia. J Mol Med 94(6):711–724. https://doi.org/10.1007/s00109-016-1387-2

    Article  CAS  PubMed  Google Scholar 

  63. Wang J, Wu D, Wang H (2019) Hydrogen Sulfide Plays an Important Protective Role by Influencing Autophagy in Diseases. Physiol Res 68(3):345. https://doi.org/10.33549/physiolres.933996

    Article  CAS  Google Scholar 

  64. Gurusamy N, Lekli I, Mukherjee S et al (2010) Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway. Cardiovasc Res 86(1):103–112. https://doi.org/10.1093/cvr/cvp384

    Article  CAS  PubMed  Google Scholar 

  65. Su F, Myers VD, Knezevic T et al (2016) Bcl-2–associated athanogene 3 protects the heart from ischemia/reperfusion injury. JCI Insight 1(19):e90931. https://doi.org/10.1172/jci.insight.90931

    Article  PubMed  PubMed Central  Google Scholar 

  66. Hu S, Cao S, Tong Z et al (2018) FGF21 protects myocardial ischemia-reperfusion injury through reduction of miR-145-mediated autophagy. Am J Transl Res 10(11):3677–3688

    CAS  PubMed  PubMed Central  Google Scholar 

  67. French CJ, Taatjes DJ, Sobel BE (2010) Autophagy in myocardium of murine hearts subjected to ischemia followed by reperfusion. Histochem Cell Biol 134(5):519–526. https://doi.org/10.1007/s00418-010-0748-0

    Article  CAS  PubMed  Google Scholar 

  68. Cao X, Wang X, Ling Y et al (2014) Comparison of the degree of autophagy in neonatal rat cardiomyocytes and H9c2 cells exposed to hypoxia/reoxygenation. Clin Lab 60(5):809–814. https://doi.org/10.7754/clin.lab.2013.130521

    Article  CAS  PubMed  Google Scholar 

  69. Gottlieb RA, Mentzer RM Jr, Linton P-J (2011) Impaired mitophagy at the heart of injury. Autophagy 7(12):1573–1574. https://doi.org/10.4161/auto.7.12.18175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lou G, Palikaras K, Lautrup S et al (2020) Mitophagy and neuroprotection. Trends Mol Med 26(1):8–20. https://doi.org/10.1016/j.molmed.2019.07.002

    Article  CAS  PubMed  Google Scholar 

  71. Tong M, Zablocki D, Sadoshima J (2020) The role of Drp1 in mitophagy and cell death in the heart. J Mol Cell Cardiol 142:138–145. https://doi.org/10.1016/j.yjmcc.2020.04.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Jin JY, Wei XX, Zhi XL et al (2020) Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin 42(5):655–664. https://doi.org/10.1038/s41401-020-00518-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Bi W, Jia J, Pang R et al (2019) Thyroid hormone postconditioning protects hearts from ischemia/reperfusion through reinforcing mitophagy. Biomed Pharmacother 118:109220. https://doi.org/10.1016/j.biopha.2019.109220

    Article  CAS  PubMed  Google Scholar 

  74. Tang W, Lin D, Chen M et al (2019) PTEN-mediated mitophagy and APE1 overexpression protects against cardiac hypoxia/reoxygenation injury. Vitr Cell Dev Biol Anim 55(9):741–748. https://doi.org/10.1007/s11626-019-00389-6

    Article  CAS  Google Scholar 

  75. Cao S, Sun Y, Wang W et al (2019) Poly (ADP-ribose) polymerase inhibition protects against myocardial ischaemia/reperfusion injury via suppressing mitophagy. J Cell Mol Med 23(10):6897–6906. https://doi.org/10.1111/jcmm.14573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Zhu N, Li J, Li Y et al (2020) Berberine protects against simulated ischemia/reperfusion injury-induced H9C2 cardiomyocytes apoptosis in vitro and myocardial ischemia/reperfusion-induced apoptosis in vivo by regulating the mitophagy-mediated HIF-1α/BNIP3 pathway. Front Pharmacol 11:367. https://doi.org/10.3389/fphar.2020.00367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wu J, Yang Y, Gao Y et al (2020) Melatonin attenuates anoxia/reoxygenation injury by inhibiting excessive mitophagy through the MT2/SIRT3/FOXO3A signaling pathway in H9C2 cells. Drug Des Dev Therapy 14:2047–2060. https://doi.org/10.2147/DDDT.S248628

    Article  CAS  Google Scholar 

  78. Zhang Y, Wang Y, Xu J et al (2019) Melatonin attenuates myocardial ischemia-reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK-OPA1 signaling pathways. J Pineal Res 66(2):e12542. https://doi.org/10.1111/jpi.12542

    Article  CAS  PubMed  Google Scholar 

  79. Sun T, Ding W, Xu T et al (2019) Parkin regulates programmed necrosis and myocardial ischemia/reperfusion injury by targeting cyclophilin-D. Antioxid Redox Signal 31(16):1177–1193. https://doi.org/10.1089/ars.2019.7734

    Article  CAS  PubMed  Google Scholar 

  80. Xin T, Lu C (2020) Irisin activates Opa1-induced mitophagy to protect cardiomyocytes against apoptosis following myocardial infarction. Aging 12(5):4474–4488. https://doi.org/10.18632/aging.102899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yu J, Li Y, Liu X et al (2019) Mitochondrial dynamics modulation as a critical contribution for Shenmai injection in attenuating hypoxia/reoxygenation injury. J Ethnopharmacol 237:9–19. https://doi.org/10.1016/j.jep.2019.03.033

    Article  CAS  PubMed  Google Scholar 

  82. Guan L, Che Z, Meng X et al (2019) MCU Up-regulation contributes to myocardial ischemia-reperfusion Injury through calpain/OPA-1–mediated mitochondrial fusion/mitophagy Inhibition. J Cell Mol Med 23(11):7830–7833. https://doi.org/10.1111/jcmm.14662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Dhanabalan K, Mzezewa S, Huisamen B et al (2020) Mitochondrial oxidative phosphorylation function and mitophagy in ischaemic/reperfused hearts from control and high-fat diet rats: effects of long-term melatonin treatment. Cardiovasc Drugs Therapy 34(6):799–811. https://doi.org/10.1007/s10557-020-06997-9

    Article  CAS  Google Scholar 

  84. Yogalingam G, Hwang S, Ferreira JCB et al (2013) Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Phosphorylation by Protein Kinase Cδ (PKCδ) Inhibits Mitochondria Elimination by Lysosomal-like structures following ischemia and reoxygenation-induced injury. J Biol Chem 288(26):18947–18960. https://doi.org/10.1074/jbc.M113.466870v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Yan L, Yang H, Li Y et al (2014) Regulator of calcineurin 1-1L protects cardiomyocytes against hypoxia-induced apoptosis via mitophagy. J Cardiovasc Pharmacol 64(4):310–317. https://doi.org/10.1097/FJC.0000000000000121

    Article  CAS  PubMed  Google Scholar 

  86. Hariharan N, Zhai P, Sadoshima J (2011) Oxidative stress stimulates autophagic flux during ischemia/reperfusion. Antioxid Redox Signal 14(11):2179–2190. https://doi.org/10.1089/ars.2010.3488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87(1):99–163. https://doi.org/10.1152/physrev.00013.2006

    Article  CAS  PubMed  Google Scholar 

  88. Naryzhnaya NV, Maslov LN, Oeltgen PR (2019) Pharmacology of mitochondrial permeability transition pore inhibitors. Drug Dev Res 80(8):1013–1030. https://doi.org/10.1002/ddr.21593

    Article  CAS  PubMed  Google Scholar 

  89. Andres AM, Stotland A, Queliconi BB et al (2015) A time to reap, a time to sow: mitophagy and biogenesis in cardiac pathophysiology. J Mol Cell Cardiol 78:62–72. https://doi.org/10.1016/j.yjmcc.2014.10.003

    Article  CAS  PubMed  Google Scholar 

  90. Kubli DA, Zhang X, Lee Y et al (2013) Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J Biol Chem 288(2):915–926. https://doi.org/10.1074/jbc.M112.411363

    Article  CAS  PubMed  Google Scholar 

  91. Zhang SX, Zhuang LL, Liu J et al (2018) The role of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction rats. Eur Rev Med Pharmacol Sci 22(15):5004–5013. https://doi.org/10.26355/eurrev_201808_15641

    Article  PubMed  Google Scholar 

  92. Li Y, Liu Z, Zhang Y et al (2018) PEDF protects cardiomyocytes by promoting FUNDC1–mediated mitophagy via PEDF-R under hypoxic condition. Int J Mol Med 41(6):3394–3404. https://doi.org/10.3892/ijmm.2018.3536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Zhao D, Sun Y, Tan Y et al (2018) Short-duration swimming exercise after myocardial infarction attenuates cardiac dysfunction and regulates mitochondrial quality control in aged mice. Oxid Med Cell Longev 2018:4079041. https://doi.org/10.1155/2018/4079041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Andres AM, Hernandez G, Lee P et al (2014) Mitophagy is required for acute cardioprotection by Simvastatin. Antioxid Redox Signal 21(14):1960–1973. https://doi.org/10.1089/ars.2013.5416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Feng Y, Zhao J, Hou H et al (2016) WDR26 promotes mitophagy of cardiomyocytes induced by hypoxia through Parkin translocation. Acta Biochim Biophys Sin (Shanghai) 48(12):1075–1084. https://doi.org/10.1093/abbs/gmw104

    Article  CAS  PubMed  Google Scholar 

  96. Hou R, Jin X, Gao Y et al (2020) Evaluation of the effects of schisandra chinensis on the myocardium of rats with hyperthyroid heart disease by using velocity vector imaging combined with the estimation of p53 Expression and calmodulin activity. Evid-Based Complement Altern Med 2020:5263834. https://doi.org/10.1155/2020/5263834

    Article  Google Scholar 

  97. Samadi A, Ziaee M, Isikhan SY et al (2020) Effects of treatment with haloperidol and clozapine on the plasma concentrations of thyroid hormones in rats. Endocr Regul 54(2):71–76. https://doi.org/10.2478/enr-2020-0009

    Article  PubMed  Google Scholar 

  98. Qiao H, Ren H, Du H et al (2018) Liraglutide repairs the infarcted heart: the role of the SIRT1/Parkin/mitophagy pathway. Mol Med Rep 17(3):3722–3734. https://doi.org/10.3892/mmr.2018.8371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Saito T, Nah J, Oka S et al (2019) An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia. J Clin Investig 129(2):802–819. https://doi.org/10.1172/JCI122035

    Article  PubMed  PubMed Central  Google Scholar 

  100. de Miranda DC, de Oliveira Faria G, Hermidorff MM et al (2021) Pre- and post-conditioning of the heart: an overview of cardioprotective signaling pathways. Curr Vasc Pharmacol 19(5):499–524. https://doi.org/10.2174/1570161119666201120160619

    Article  CAS  PubMed  Google Scholar 

  101. Tsibulnikov SY, Maslov LN, Gorbunov AS et al (2019) A review of humoral factors in remote preconditioning of the heart. J Cardiovasc Pharmacol Therapy 24(5):403–421. https://doi.org/10.1177/1074248419841632

    Article  CAS  Google Scholar 

  102. Gurusamy N, Lekli I, Gorbunov NV et al (2009) Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein. J Cell Mol Med 13(2):373–387. https://doi.org/10.1111/j.1582-4934.2008.00495.x

    Article  PubMed  Google Scholar 

  103. Gedik N, Thielmann M, Kottenberg E et al (2014) No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting. PLoS ONE 9(5):e96567. https://doi.org/10.1371/journal.pone.0096567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Rohailla S, Clarizia N, Sourour M et al (2014) Acute, delayed and chronic remote ischemic conditioning is associated with downregulation of mTOR and enhanced autophagy signaling. PLoS ONE 9(10):e111291. https://doi.org/10.1371/journal.pone.0111291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Wagner C, Tillack D, Simonis G et al (2010) Ischemic post-conditioning reduces infarct size of the in vivo rat heart: role of PI3-K, mTOR, GSK-3β, and apoptosis. Mol Cell Biochem 339(1–2):135–147. https://doi.org/10.1007/s11010-009-0377-x

    Article  CAS  PubMed  Google Scholar 

  106. Wei C, Li H, Han L et al (2013) Activation of autophagy in ischemic postconditioning contributes to cardioprotective effects against ischemia/reperfusion injury in rat hearts. J Cardiovasc Pharmacol 61(5):416–422. https://doi.org/10.1097/FJC.0b013e318287d501

    Article  CAS  PubMed  Google Scholar 

  107. Hao M, Zhu S, Hu L et al (2017) Myocardial ischemic postconditioning promotes autophagy against ischemia reperfusion injury via the activation of the nNOS/AMPK/mTOR pathway. Int J Mol Sci 18(3):614. https://doi.org/10.3390/ijms18030614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Tyagi S, Singh N, Virdi J et al (2019) Diabetes abolish cardioprotective effects of remote ischemic conditioning: evidences and possible mechanisms. J Physiol Biochem 75:19–28. https://doi.org/10.1007/s13105-019-00664-w

    Article  CAS  PubMed  Google Scholar 

  109. Han Z, Cao J, Song D et al (2014) Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice. PLoS ONE 9(1):e86838. https://doi.org/10.1371/journal.pone.0086838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Krylatov AV, Maslov LN, Voronkov NS et al (2018) Reactive oxygen species as intracellular signaling molecules in the cardiovascular system. Curr Cardiol Rev 14(4):290–300. https://doi.org/10.2174/1573403X14666180702152436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Liu L, Jin X, Hu C-F et al (2017) Exosomes derived from mesenchymal stem cells rescue myocardial ischaemia/reperfusion injury by inducing cardiomyocyte autophagy Via AMPK and Akt pathways. Cell Physiol Biochem 43(1):52–68. https://doi.org/10.1159/000480317

    Article  CAS  PubMed  Google Scholar 

  112. Sciarretta S, Zhai P, Shao D et al (2013) Activation of NADPH oxidase 4 in the endoplasmic reticulum promotes cardiomyocyte autophagy and survival during energy stress through the protein kinase RNA-activated-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcripti. Circ Res 113(11):1253–1264. https://doi.org/10.1161/CIRCRESAHA.113.301787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Shiomi M, Miyamae M, Takemura G et al (2014) Sevoflurane induces cardioprotection through reactive oxygen species-mediated upregulation of autophagy in isolated guinea pig hearts. J Anesth 28(4):593–600. https://doi.org/10.1007/s00540-013-1755-9

    Article  PubMed  Google Scholar 

  114. Wang S, Wang C, Yan F et al (2017) N-acetylcysteine attenuates diabetic myocardial ischemia reperfusion injury through inhibiting excessive autophagy. Mediators Inflamm 2017:9257291. https://doi.org/10.1155/2017/9257291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Li D, Wang J, Hou J et al (2016) Salvianolic acid B induced upregulation of miR-30a protects cardiac myocytes from ischemia/reperfusion injury. BMC Complement Altern Med 16(1):336. https://doi.org/10.1186/s12906-016-1275-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Wang Z-G, Li H, Huang Y et al (2017) Nerve growth factor-induced Akt/mTOR activation protects the ischemic heart via restoring autophagic flux and attenuating ubiquitinated protein accumulation. Oncotarget 8(3):5400–5413. https://doi.org/10.18632/oncotarget.14284

    Article  PubMed  Google Scholar 

  117. Li X, Hu X, Wang J et al (2018) Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury. Int J Mol Med 42(4):1917–1924. https://doi.org/10.3892/ijmm.2018.3794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Qin L, Fan S, Jia R et al (2018) Ginsenoside Rg1 protects cardiomyocytes from hypoxia-induced injury through the PI3K/AKT/mTOR pathway. Pharmazie 73(6):349–355. https://doi.org/10.1691/ph.2018.8329

    Article  CAS  PubMed  Google Scholar 

  119. Matsui Y, Takagi H, Qu X et al (2007) Distinct roles of autophagy in the heart during ischemia and reperfusion. Circ Res 100(6):914–922. https://doi.org/10.1161/01.RES.0000261924.76669.36

    Article  CAS  PubMed  Google Scholar 

  120. Huang L, Dai K, Chen M et al (2016) The AMPK agonist PT1 and mTOR inhibitor 3HOI-BA-01 protect cardiomyocytes after ischemia through induction of autophagy. J Cardiovasc Pharmacol Ther 21(1):70–81. https://doi.org/10.1177/1074248415581177

    Article  CAS  PubMed  Google Scholar 

  121. Zhang H, Liu B, Li T et al (2017) AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia. Int J Mol Med 41(1):69–76. https://doi.org/10.3892/ijmm.2017.3213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Zhai P, Sciarretta S, Galeotti J et al (2011) Differential roles of GSK-3β during myocardial ischemia and ischemia/reperfusion. Circ Res 109(5):502–511. https://doi.org/10.1161/CIRCRESAHA.111.249532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Sciarretta S, Volpe M, Sadoshima J (2014) Mammalian target of rapamycin signaling in cardiac physiology and disease. Circ Res 114(3):549–564. https://doi.org/10.1161/CIRCRESAHA.114.302022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Aoyagi T, Kusakari Y, Xiao C-Y et al (2012) Cardiac mTOR protects the heart against ischemia-reperfusion injury. Am J Physiol Circ Physiol 303(1):H75–H85. https://doi.org/10.1152/ajpheart.00241.2012

    Article  CAS  Google Scholar 

  125. Zhang D, He Y, Ye X et al (2020) Activation of autophagy inhibits nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome activation and attenuates myocardial ischemia-reperfusion injury in diabetic rats. J Diabetes Investig 11(5):1126–1136. https://doi.org/10.1111/jdi.13235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Xu J, Qin X, Cai X et al (2015) Mitochondrial JNK activation triggers autophagy and apoptosis and aggravates myocardial injury following ischemia/reperfusion. Biochim Biophys Acta Mol Basis Dis 1852(2):262–270. https://doi.org/10.1016/j.bbadis.2014.05.012

    Article  CAS  Google Scholar 

  127. Giricz Z, Varga ZV, Koncsos G et al (2017) Autophagosome formation is required for cardioprotection by chloramphenicol. Life Sci 186:11–16. https://doi.org/10.1016/j.lfs.2017.07.0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Bian X, Teng T, Zhao H et al (2018) Zinc prevents mitochondrial superoxide generation by inducing mitophagy in the setting of hypoxia/reoxygenation in cardiac cells. Free Radic Res 52(1):80–91. https://doi.org/10.1080/10715762.2017.1414949

    Article  CAS  PubMed  Google Scholar 

  129. Lu Y, Bu M, Yun H (2019) Sevoflurane prevents hypoxia/reoxygenation-induced cardiomyocyte apoptosis by inhibiting PI3KC3-mediated autophagy. Hum Cell 32(2):150–159. https://doi.org/10.1007/s13577-018-00230-4

    Article  CAS  PubMed  Google Scholar 

  130. Yi RF, Lin JZ, Cui L et al (2019) Role of hexokinase II in the changes of autophagic flow in cardiomyocytes of mice with ischemia-hypoxia in vitro. Zhonghua Shao Shang Za Zhi 35(2):116–124. https://doi.org/10.3760/cma.j.issn.1009-2587.2019.02.007

    Article  CAS  PubMed  Google Scholar 

  131. Chen L, Hahn H, Wu G et al (2001) Opposing cardioprotective actions and parallel hypertrophic effects of delta PKC and epsilon PKC. Proc Natl Acad Sci USA 98(20):11114–11119. https://doi.org/10.1073/pnas.191369098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Dang M, Zeng X, Chen B et al (2019) Soluble receptor for advance glycation end-products inhibits ischemia/reperfusion-induced myocardial autophagy via the STAT3 pathway. Free Radic Biol Med 130:107–119. https://doi.org/10.1016/j.freeradbiomed.2018.10.437

    Article  CAS  PubMed  Google Scholar 

  133. McCormick J, Suleman N, Scarabelli TM et al (2012) STAT1 deficiency in the heart protects against myocardial infarction by enhancing autophagy. J Cell Mol Med 16(2):386–393. https://doi.org/10.1111/j.1582-4934.2011.01323.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Hoshino A, Matoba S, Iwai-Kanai E et al (2012) p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia. J Mol Cell Cardiol 52(1):175–184. https://doi.org/10.1016/j.yjmcc.2011.10.008

    Article  CAS  PubMed  Google Scholar 

  135. Zeng M, Wei X, Wu Z et al (2013) NF-κB-mediated induction of autophagy in cardiac ischemia/reperfusion injury. Biochem Biophys Res Commun 436(2):180–185. https://doi.org/10.1016/j.bbrc.2013.05.070

    Article  CAS  PubMed  Google Scholar 

  136. Gui L, Liu B, Lv G (2016) Hypoxia induces autophagy in cardiomyocytes via a hypoxia-inducible factor 1-dependent mechanism. Exp Ther Med 11(6):2233–2239. https://doi.org/10.3892/etm.2016.3190

    Article  PubMed  PubMed Central  Google Scholar 

  137. Zhao M, Zhu P, Fujino M et al (2016) 5-Aminolevulinic acid with sodium ferrous citrate induces autophagy and protects cardiomyocytes from hypoxia-induced cellular injury through MAPK-Nrf-2-HO-1 signaling cascade. Biochem Biophys Res Commun 479(4):663–669. https://doi.org/10.1016/j.bbrc.2016.09.156

    Article  CAS  PubMed  Google Scholar 

  138. Cortes CJ, La Spada AR (2019) TFEB dysregulation as a driver of autophagy dysfunction in neurodegenerative disease: Molecular mechanisms, cellular processes, and emerging therapeutic opportunities. Neurobiol Dis 122:83–93. https://doi.org/10.1016/j.nbd.2018.05.012

    Article  CAS  PubMed  Google Scholar 

  139. Pan B, Zhang H, Cui T et al (2017) TFEB activation protects against cardiac proteotoxicity via increasing autophagic flux. J Mol Cell Cardiol 113:51–62. https://doi.org/10.1016/j.yjmcc.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Song H, Feng X, Zhang H et al (2019) METTL3 and ALKBH5 oppositely regulate m6A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes. Autophagy 15(8):1419–1437. https://doi.org/10.1080/15548627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Godar RJ, Ma X, Liu H et al (2015) Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury. Autophagy 11(9):1537–1560. https://doi.org/10.1080/15548627.2015.1063768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. van der Pol E, Böing AN, Harrison P et al (2012) Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 64(3):676–705. https://doi.org/10.1124/pr.112.005983

    Article  CAS  PubMed  Google Scholar 

  143. Sluijter JPG, Davidson SM, Boulanger CM et al (2018) Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res 114(1):19–34. https://doi.org/10.1093/cvr/cvx211

    Article  CAS  PubMed  Google Scholar 

  144. Colombo M, Raposo G, Théry C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30(1):255–289. https://doi.org/10.1146/annurev-cellbio-101512-122326

    Article  CAS  PubMed  Google Scholar 

  145. Valadi H, Valadi A, Adler L et al (2001) An improved gas distribution system for anaerobic screening of multiple microbial cultures. J Microbiol Methods 47(1):51–57. https://doi.org/10.1016/s0167-7012(01)00288-3

    Article  CAS  PubMed  Google Scholar 

  146. Skog J, Würdinger T, van Rijn S et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476. https://doi.org/10.1038/ncb1800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Hunter MP, Ismail N, Zhang X et al (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE 3(11):e3694. https://doi.org/10.1371/journal.pone.0003694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Valadi H, Ekström K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659. https://doi.org/10.1038/ncb1596

    Article  CAS  PubMed  Google Scholar 

  149. Gupta S, Knowlton AA (2007) HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. Am J Physiol Circ Physiol 292(6):H3052–H3056. https://doi.org/10.1152/ajpheart.01355.2006

    Article  CAS  Google Scholar 

  150. Bang C, Batkai S, Dangwal S et al (2014) Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Investig 124(5):2136–2146. https://doi.org/10.1172/JCI70577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. van Balkom BWM, de Jong OG, Smits M et al (2013) Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood 121(19):3997–4006. https://doi.org/10.1182/blood-2013-02-478925

    Article  CAS  PubMed  Google Scholar 

  152. Jiang X-X, Liu G-Y, Lei H et al (2018) Activation of transient receptor potential vanilloid 1 protects the heart against apoptosis in ischemia/reperfusion injury through upregulating the PI3K/Akt signaling pathway. Int J Mol Med 41(3):1724–1730. https://doi.org/10.3892/ijmm.2017.3338

    Article  CAS  PubMed  Google Scholar 

  153. Fromm B, Billipp T, Peck LE et al (2015) A uniform system for the annotation of vertebrate microRNA genes and the evolution of the human microRNAome. Annu Rev Genet 49(1):213–242. https://doi.org/10.1146/annurev-genet-120213-092023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Xiao J, Zhu X, He B et al (2011) MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II. J Biomed Sci 18(1):35. https://doi.org/10.1186/1423-0127-18-35

    Article  PubMed  PubMed Central  Google Scholar 

  155. Bo L, Su-Ling D, Fang L et al (2014) Autophagic program is regulated by miR-325. Cell Death Differ 21(6):967–977. https://doi.org/10.1038/cdd.2014.18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Li J, Rohailla S, Gelber N et al (2014) MicroRNA-144 is a circulating effector of remote ischemic preconditioning. Basic Res Cardiol 109(5):423. https://doi.org/10.1007/s00395-014-0423-z

    Article  CAS  PubMed  Google Scholar 

  157. Li X, Zeng Z, Li Q et al (2015) Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in cardiomyocytes by suppressing cell apoptosis and enhancing autophagy. Oncotarget 6(22):18829–18844. https://doi.org/10.18632/oncotarget.4774

    Article  PubMed  PubMed Central  Google Scholar 

  158. Chen Q, Zhou Y, Richards AM et al (2016) Up-regulation of miRNA-221 inhibits hypoxia/reoxygenation-induced autophagy through the DDIT4/mTORC1 and Tp53inp1/p62 pathways. Biochem Biophys Res Commun 474(1):168–174. https://doi.org/10.1016/j.bbrc.2016.04.090

    Article  CAS  PubMed  Google Scholar 

  159. Zhao P, Zhang BL, Liu K et al (2018) Overexpression of miR-638 attenuated the effects of hypoxia/reoxygenation treatment on cell viability, cell apoptosis and autophagy by targeting ATG5 in the human cardiomyocytes. Eur Rev Med Pharmacol Sci 22(23):8462–8471. https://doi.org/10.26355/eurrev_201812_16546

    Article  CAS  PubMed  Google Scholar 

  160. Shao H, Yang L, Wang L et al (2018) MicroRNA-34a protects myocardial cells against ischemia–reperfusion injury through inhibiting autophagy via regulating TNFα expression. Biochem Cell Biol 96(3):349–354. https://doi.org/10.1139/bcb-2016-0158

    Article  CAS  PubMed  Google Scholar 

  161. Liu X, Deng Y, Xu Y et al (2018) MicroRNA-223 protects neonatal rat cardiomyocytes and H9c2 cells from hypoxia-induced apoptosis and excessive autophagy via the Akt/mTOR pathway by targeting PARP-1. J Mol Cell Cardiol 118:133–146. https://doi.org/10.1016/j.yjmcc.2018.03.018

    Article  CAS  PubMed  Google Scholar 

  162. Zhang C, Zhang C, Wang H et al (2019) Effects of miR–103a–3p on the autophagy and apoptosis of cardiomyocytes by regulating Atg5. Int J Mol Med 43(5):1951–1960. https://doi.org/10.3892/ijmm.2019.4128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Zhu Q, Hu F (2019) Antagonism of miR-429 ameliorates anoxia/reoxygenation injury in cardiomyocytes by enhancing MO25/LKB1/AMPK mediated autophagy. Life Sci 235:116842. https://doi.org/10.1016/j.lfs.2019.116842

    Article  CAS  PubMed  Google Scholar 

  164. Hung T, Chang HY (2010) Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol 7(5):582–585. https://doi.org/10.4161/rna.7.5.13216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Yoon J-H, Abdelmohsen K, Gorospe M (2013) Posttranscriptional gene regulation by long noncoding RNA. J Mol Biol 425(19):3723–3730. https://doi.org/10.1016/j.jmb.2012.11.024

    Article  CAS  PubMed  Google Scholar 

  166. Huang Z, Ye B, Wang Z et al (2018) Inhibition of LncRNA-HRIM increases cell viability by regulating autophagy levels during hypoxia/reoxygenation in myocytes. Cell Physiol Biochem 46(4):1341–1351. https://doi.org/10.1159/000489149

    Article  CAS  PubMed  Google Scholar 

  167. Ma M, Hui J, Zhang Q et al (2018) Long non-coding RNA nuclear-enriched abundant transcript 1 inhibition blunts myocardial ischemia reperfusion injury via autophagic flux arrest and apoptosis in streptozotocin-induced diabetic rats. Atherosclerosis 277:113–122. https://doi.org/10.1016/j.atherosclerosis.2018.08.031

    Article  CAS  PubMed  Google Scholar 

  168. Kong F, Jin J, Lv X et al (2019) Long noncoding RNA RMRP upregulation aggravates myocardial ischemia-reperfusion injury by sponging miR-206 to target ATG3 expression. Biomed Pharmacother 109:716–725. https://doi.org/10.1016/j.biopha.2018.10.079

    Article  CAS  PubMed  Google Scholar 

  169. Maslov LN, Mukhomedzyanov AV, Sementsov AS (2017) Trigger and signal mechanisms and the end effector of the cardioprotective effect of remote postconditioning of the heart. Neurosci Behav Physiol 47(2):186–189. https://doi.org/10.1007/s11055-016-0384-9

    Article  Google Scholar 

  170. Yu X, Ge L, Niu L et al (2018) The dual role of inducible nitric oxide synthase in myocardial ischemia/reperfusion injury: friend or foe? Oxid Med Cell Longev 2018:1–7. https://doi.org/10.1155/2018/8364848

    Article  CAS  Google Scholar 

  171. Rabkin SW (2007) Nitric oxide-induced cell death in the heart: the role of autophagy. Autophagy 3(4):347–349. https://doi.org/10.4161/auto.4054

    Article  CAS  PubMed  Google Scholar 

  172. Yuan H, Perry CN, Huang C et al (2009) LPS-induced autophagy is mediated by oxidative signaling in cardiomyocytes and is associated with cytoprotection. Am J Physiol Circ Physiol 296(2):H470–H479. https://doi.org/10.1152/ajpheart.01051.2008

    Article  CAS  Google Scholar 

  173. Lin L, Xu J, Ye Y et al (2015) Isosorbide dinitrate inhibits mechanical stress-induced cardiac hypertrophy and autophagy through downregulation of angiotensin II type 1 receptor. J Cardiovasc Pharmacol 65(1):1–7. https://doi.org/10.1097/FJC.0000000000000122

    Article  CAS  PubMed  Google Scholar 

  174. Cao J, Xie H, Sun Y et al (2015) Sevoflurane post-conditioning reduces rat myocardial ischemia reperfusion injury through an increase in NOS and a decrease in phopshorylated NHE1 levels. Int J Mol Med 36(6):1529–1537. https://doi.org/10.3892/ijmm.2015.2366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Qiao S, Sun Y, Sun B et al (2019) Sevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism. Acta Pharmacol Sin 40(1):35–45. https://doi.org/10.1038/s41401-018-0066-y

    Article  CAS  PubMed  Google Scholar 

  176. Ryter SW, Ma KC, Choi AMK (2018) Carbon monoxide in lung cell physiology and disease. Am J Physiol Physiol 314(2):C211–C227. https://doi.org/10.1152/ajpcell.00022.2017

    Article  CAS  Google Scholar 

  177. Chen D, Jin Z, Zhang J et al (2016) HO-1 protects against hypoxia/reoxygenation-induced mitochondrial dysfunction in H9c2 cardiomyocytes. PLoS ONE 11(5):e0153587. https://doi.org/10.1371/journal.pone.0153587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Zhang Q-Y, Jin H-F, Chen S et al (2018) Hydrogen sulfide regulating myocardial structure and function by targeting cardiomyocyte autophagy. Chin Med J 131(7):839–844. https://doi.org/10.4103/0366-6999.228249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Osipov RM, Robich MP, Feng J et al (2009) Effect of hydrogen sulfide in a porcine model of myocardial ischemia-reperfusion: comparison of different administration regimens and characterization of the cellular mechanisms of protection. J Cardiovasc Pharmacol 54(4):287–297. https://doi.org/10.1097/FJC.0b013e3181b2b72b

    Article  CAS  PubMed  Google Scholar 

  180. Osipov RM, Robich MP, Feng J et al (2010) Effect of hydrogen sulfide on myocardial protection in the setting of cardioplegia and cardiopulmonary bypass. Interact Cardiovasc Thorac Surg 10(4):506–512. https://doi.org/10.1510/icvts.2009.219535

    Article  PubMed  Google Scholar 

  181. Xie H, Xu Q, Jia J et al (2015) Hydrogen sulfide protects against myocardial ischemia and reperfusion injury by activating AMP-activated protein kinase to restore autophagic flux. Biochem Biophys Res Commun 458(3):632–638. https://doi.org/10.1016/j.bbrc.2015.02.017

    Article  CAS  PubMed  Google Scholar 

  182. Jiang H, Xiao J, Kang B et al (2016) PI3K/SGK1/GSK3β signaling pathway is involved in inhibition of autophagy in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation by hydrogen sulfide. Exp Cell Res 345(2):134–140. https://doi.org/10.1016/j.yexcr.2015.07.005

    Article  CAS  PubMed  Google Scholar 

  183. Xiao J, Zhu X, Kang B et al (2015) Hydrogen sulfide attenuates myocardial hypoxia-reoxygenation injury by inhibiting autophagy via mTOR activation. Cell Physiol Biochem 37(6):2444–2453. https://doi.org/10.1159/000438597

    Article  CAS  PubMed  Google Scholar 

  184. Liang B, Xiao T, Long J et al (2017) Hydrogen sulfide alleviates myocardial fibrosis in mice with alcoholic cardiomyopathy by downregulating autophagy. Int J Mol Med 40(6):1781–1791. https://doi.org/10.3892/ijmm.2017.3191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Bai Y, Yang Y, Mu X et al (2018) Hydrogen sulfide alleviates acute myocardial ischemia injury by modulating autophagy and inflammation response under oxidative stress. Oxid Med Cell Longev 2018:1–17. https://doi.org/10.1155/2018/3402809

    Article  CAS  Google Scholar 

  186. Chen J, Gao J, Sun W et al (2016) Involvement of exogenous H2S in recovery of cardioprotection from ischemic post-conditioning via increase of autophagy in the aged hearts. Int J Cardiol 220:681–692. https://doi.org/10.1016/j.ijcard.2016.06.200

    Article  PubMed  Google Scholar 

  187. Sciarretta S, Zhai P, Shao D et al (2012) Rheb is a critical regulator of autophagy during myocardial ischemia. Circulation 125(9):1134–1146. https://doi.org/10.1161/CIRCULATIONAHA.111.078212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Chen HH, Mekkaoui C, Cho H et al (2013) Fluorescence tomography of rapamycin-induced autophagy and cardioprotection in vivo. Circ Cardiovasc Imaging 6(3):441–447. https://doi.org/10.1161/CIRCIMAGING.112.000074

    Article  PubMed  PubMed Central  Google Scholar 

  189. Yang S-S, Liu Y-B, Yu J-B et al (2010) Rapamycin protects heart from ischemia/reperfusion injury independent of autophagy by activating PI3 kinase-Akt pathway and mitochondria K(ATP) channel. Pharmazie 65(10):760–765. https://doi.org/10.1691/ph.2010.0576

    Article  CAS  PubMed  Google Scholar 

  190. Loos B, Genade S, Ellis B et al (2011) At the core of survival: autophagy delays the onset of both apoptotic and necrotic cell death in a model of ischemic cell injury. Exp Cell Res 317(10):1437–1453. https://doi.org/10.1016/j.yexcr.2011.03.011

    Article  CAS  PubMed  Google Scholar 

  191. Zeng C, Li H, Fan Z et al (2016) Crocin-elicited autophagy rescues myocardial ischemia/reperfusion injury via paradoxical mechanisms. Am J Chin Med 44(3):515–530. https://doi.org/10.1142/S0192415X16500282

    Article  CAS  PubMed  Google Scholar 

  192. Hermann R, Vélez DE, Rusiecki TM et al (2015) Effects of 3-methyladenine on isolated left atria subjected to simulated ischaemia-reperfusion. Clin Exp Pharmacol Physiol 42(1):41–51. https://doi.org/10.1111/1440-1681.12323

    Article  CAS  PubMed  Google Scholar 

  193. Zhou B, Leng Y, Lei SQ et al (2017) AMPK activation restores ischemic post-conditioning cardioprotection in STZ-induced type 1 diabetic rats: Role of autophagy. Mol Med Rep 16(3):3648–3656. https://doi.org/10.3892/mmr.2017.7033

    Article  CAS  PubMed  Google Scholar 

  194. Ling Y, Chen G, Deng Y et al (2016) Polydatin post-treatment alleviates myocardial ischaemia/reperfusion injury by promoting autophagic flux. Clin Sci 130(18):1641–1653. https://doi.org/10.1042/CS20160082

    Article  CAS  Google Scholar 

  195. Przyklenk K, Undyala VVR, Wider J et al (2011) Acute induction of autophagy as a novel strategy for cardioprotection: getting to the heart of the matter. Autophagy 7:432–433. https://doi.org/10.4161/auto.7.4.14395

    Article  PubMed  PubMed Central  Google Scholar 

  196. Yang K, Xu C, Li X et al (2013) Combination of D942 with curcumin protects cardiomyocytes from ischemic damage through promoting autophagy. J Cardiovasc Pharmacol Therapy 18(6):570–581. https://doi.org/10.1177/1074248413503495

    Article  CAS  Google Scholar 

  197. Wu X, He L, Cai Y et al (2013) Induction of autophagy contributes to the myocardial protection of valsartan against ischemia-reperfusion injury. Mol Med Rep 8(6):1824–1830. https://doi.org/10.3892/mmr.2013.1708

    Article  CAS  PubMed  Google Scholar 

  198. Xie M, Kong Y, Tan W et al (2014) Histone deacetylase inhibition blunts ischemia/reperfusion injury by inducing cardiomyocyte autophagy. Circulation 129(10):1139–1151. https://doi.org/10.1161/CIRCULATIONAHA.113.002416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Wu X, Zheng D, Qin Y et al (2017) Nobiletin attenuates adverse cardiac remodeling after acute myocardial infarction in rats via restoring autophagy flux. Biochem Biophys Res Commun 492(2):262–268. https://doi.org/10.1016/j.bbrc.2017.08.064

    Article  CAS  PubMed  Google Scholar 

  200. Zhang J, Nadtochiy SM, Urciuoli WR et al (2016) The cardioprotective compound cloxyquin uncouples mitochondria and induces autophagy. Am J Physiol Heart Circ Physiol 310(1):H29–H38. https://doi.org/10.1152/ajpheart.00926.2014

    Article  PubMed  Google Scholar 

  201. Liu L, Wu Y, Huang X (2016) Orientin protects myocardial cells against hypoxia-reoxygenation injury through induction of autophagy. Eur J Pharmacol 776:90–98. https://doi.org/10.1016/j.ejphar.2016.02.037

    Article  CAS  PubMed  Google Scholar 

  202. Ma Y, Gai Y, Yan J et al (2016) Puerarin attenuates anoxia/reoxygenation injury through enhancing Bcl-2 associated athanogene 3 expression, a modulator of apoptosis and autophagy. Med Sci Monit 22:977–983. https://doi.org/10.12659/msm.897379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Zhao R, Xie E, Yang X et al (2019) Alliin alleviates myocardial ischemia-reperfusion injury by promoting autophagy. Biochem Biophys Res Commun 512(2):236–243. https://doi.org/10.1016/j.bbrc.2019.03.046

    Article  CAS  PubMed  Google Scholar 

  204. Ren Z, Xiao W, Zeng Y et al (2019) Fibroblast growth factor-21 alleviates hypoxia/reoxygenation injury in H9c2 cardiomyocytes by promoting autophagic flux. Int J Mol Med 43(3):1321–1330. https://doi.org/10.3892/ijmm.2019.4071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Yan J, Yan JY, Wang YX et al (2019) Spermidine-enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway. Br J Pharmacol 176(17):3126–3142. https://doi.org/10.1111/bph.14706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Meyer G, Czompa A, Reboul C et al (2013) The cellular autophagy markers beclin-1 and LC3B-II are increased during reperfusion in fibrillated mouse hearts. Curr Pharm Des 19(39):6912–6918. https://doi.org/10.2174/138161281939131127122510

    Article  CAS  PubMed  Google Scholar 

  207. Cao X, Chen A, Yang P et al (2013) Alpha-lipoic acid protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy. Biochem Biophys Res Commun 441(4):935–940. https://doi.org/10.1016/j.bbrc.2013.10.166

    Article  CAS  PubMed  Google Scholar 

  208. Bouhidel JO, Wang P, Siu KL et al (2015) Netrin-1 improves post-injury cardiac function in vivo via DCC/NO-dependent preservation of mitochondrial integrity, while attenuating autophagy. Biochim Biophys Acta Mol Basis Dis 1852(2):277–289. https://doi.org/10.1016/j.bbadis.2014.06.005

    Article  CAS  Google Scholar 

  209. Xiao J, Zhu X, Ji G et al (2014) Ulinastatin protects cardiomyocytes against ischemia-reperfusion injury by regulating autophagy through mTOR activation. Mol Med Rep 10(4):1949–1953. https://doi.org/10.3892/mmr.2014.2450

    Article  CAS  PubMed  Google Scholar 

  210. Yao T, Ying X, Zhao Y et al (2015) Vitamin D receptor activation protects against myocardial reperfusion injury through inhibition of apoptosis and modulation of autophagy. Antioxid Redox Signal 22(8):633–650. https://doi.org/10.1089/ars.2014.5887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Jia Z, Lin L, Huang S et al (2017) Inhibition of autophagy by berberine enhances the survival of H9C2 myocytes following hypoxia. Mol Med Rep 16(2):1677–1684. https://doi.org/10.3892/mmr.2017.6770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Xie H, Liu Q, Qiao S et al (2015) Delayed cardioprotection by sevoflurane preconditioning: a novel mechanism via inhibiting Beclin 1-mediated autophagic cell death in cardiac myocytes exposed to hypoxia/reoxygenation injury. Int J Clin Exp Pathol 8(1):217–226

    PubMed  PubMed Central  Google Scholar 

  213. Sun Z, Han J, Zhao W et al (2014) TRPV1 activation exacerbates hypoxia/reoxygenation-induced apoptosis in H9C2 cells via calcium overload and mitochondrial dysfunction. Int J Mol Sci 15(10):18362–18380. https://doi.org/10.3390/ijms151018362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Wang B, Zhong S, Zheng F et al (2015) N-n-butyl haloperidol iodide protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy. Oncotarget 6(28):24709–24721. https://doi.org/10.18632/oncotarget.5077

    Article  PubMed  PubMed Central  Google Scholar 

  215. Zhou LY, Zhai M, Huang Y et al (2019) The circular RNA ACR attenuates myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the Pink1/ FAM65B pathway. Cell Death Differ 26(7):1299–1315. https://doi.org/10.1038/s41418-018-0206-4

    Article  CAS  PubMed  Google Scholar 

  216. Zuo Z, Zuo P, Sheng Z et al (2019) Tetramethylprazine attenuates myocardial ischemia/reperfusion injury through modulation of autophagy. Life Sci 239:117016. https://doi.org/10.1016/j.lfs.2019.117016

    Article  CAS  PubMed  Google Scholar 

  217. Jin P, Li L-H, Shi Y et al (2020) Salidroside inhibits apoptosis and autophagy of cardiomyocyte by regulation of circular RNA hsa_circ_0000064 in cardiac ischemia-reperfusion injury. Gene 767:145075. https://doi.org/10.1016/j.gene.2020.145075

    Article  CAS  PubMed  Google Scholar 

  218. Liu TJ, Yeh YC, Lee WL et al (2020) Insulin ameliorates hypoxia-induced autophagy, endoplasmic reticular stress and apoptosis of myocardial cells: In vitro and ex vivo models. Eur J Pharmacol 880:173125. https://doi.org/10.1016/j.ejphar.2020.173125

    Article  CAS  PubMed  Google Scholar 

  219. Yue LJ, Zhu XY, Li RS et al (2019) S-allyl-cysteine sulfoxide (alliin) alleviates myocardial infarction by modulating cardiomyocyte necroptosis and autophagy. Int J Mol Med 44(5):1943–1951. https://doi.org/10.3892/ijmm.2019.4351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Li C, Mu N, Gu C et al (2020) Metformin mediates cardioprotection against aging-induced ischemic necroptosis. Aging Cell 19(2):e13096. https://doi.org/10.1111/acel.13096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This article was supported of by state assignment 122020300042-4.

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Authors and Affiliations

  1. Cardiology Research Institute, Tomsk National Research Medical Centre, the Russian Academy of Sciences, Tomsk, Russia, 634012

    Sergey V. Popov, Alexander V. Mukhomedzyanov, Nikita S. Voronkov, Ivan A. Derkachev, Alla A. Boshchenko & Leonid N. Maslov

  2. School of Basic Medicine, Fourth Military Medical University, No.169, West Changle Road, Xi’an, 710032, China

    Feng Fu

  3. Tyumen State Medical University, Tyumen, Russia, 625023

    Galina Z. Sufianova & Maria S. Khlestkina

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  1. Sergey V. Popov
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SVP verification of critical intellectual content, article editing. AVM and NSV searching for published data on the subject of an article, writing and typing of articles, preparation for publishing. IAD preparing figures. AAB, FF, GZS and MSK verification of critical intellectual content. LNM devised the project, the main conceptual ideas of the article, final approval of the content for publication of the manuscript. All authors read and approved the final manuscript.

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Popov, S.V., Mukhomedzyanov, A.V., Voronkov, N.S. et al. Regulation of autophagy of the heart in ischemia and reperfusion. Apoptosis 28, 55–80 (2023). https://doi.org/10.1007/s10495-022-01786-1

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