Shock Wave Therapy Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Ferroptosis.

Jiannan Wang, Na Jia, Kaiyi Zhu, Kun Xu, Mingjing Yan, Ming Lan, Junmeng Liu, Bing Liu, Tao Shen, Qing He
Author Information
  1. Jiannan Wang: Department of Cardiology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing 100730, China. ORCID
  2. Na Jia: Department of Cardiology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing 100730, China. ORCID
  3. Kaiyi Zhu: Department of Cardiology Shanxi Bethune Hospital Shanxi Academy of Medical Sciences Tongji Shanxi Hospital Third Hospital of Shanxi Medical University, Taiyuan 030032, China. ORCID
  4. Kun Xu: Graduate School of Peking Union Medical College, Beijing, China.
  5. Mingjing Yan: The Key Laboratory of Geriatrics Beijing Institute of Geriatrics Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China.
  6. Ming Lan: Department of Cardiology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing 100730, China. ORCID
  7. Junmeng Liu: Department of Cardiology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing 100730, China.
  8. Bing Liu: Department of Cardiology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing 100730, China. ORCID
  9. Tao Shen: The Key Laboratory of Geriatrics Beijing Institute of Geriatrics Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China. ORCID
  10. Qing He: Department of Cardiology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing 100730, China. ORCID

Abstract

Shock wave therapy (SWT) is a new alternative therapy for patients with severe coronary artery disease that improves myocardial ischemic symptoms by delivering low-energy shock wave stimulation to ischaemic myocardium with low-energy pulsed waves. However, the specific mechanism of its protective effect is not fully understood, especially for the protective mechanism in cardiomyocytes after hypoxia/reoxygenation (H/R). We selected a rat H9c2 cardiomyocyte cell line to establish a stable H/R cardiomyocyte injury model by hypoxia/reoxygenation, and then used SWT for therapeutic intervention to explore its cardiomyocyte protective mechanisms. The results showed that SWT significantly increased cell viability and GSH levels while decreasing LDH levels, ROS levels, and MDA levels. SWT also improved mitochondrial morphology and function of cells after H/R. Meanwhile, we found that SWT could increase the expression of GPX4, xCT, and Bcl-2, while decreasing the expression of Bax and cleaved caspase-3, and inhibiting cardiomyocyte apoptosis and ferroptosis. Moreover, this protective effect of SWT on cardiomyocytes could be significantly reversed by knockdown of xCT, a key regulator protein of ferroptosis. In conclusion, our study shows that SWT can attenuate hypoxia-reoxygenation-induced myocardial injury and protect cardiomyocyte function by inhibiting H/R-induced apoptosis and ferroptosis, and this therapy may have important applications in the treatment of clinical myocardial ischemic diseases.

References

  1. Am J Cardiol. 2021 Apr 1;144:26-32 [PMID: 33385348]
  2. Pharmacol Res. 2021 Apr;166:105466 [PMID: 33548489]
  3. Bioengineered. 2021 Dec;12(2):10924-10934 [PMID: 34699317]
  4. Oncotarget. 2017 Dec 8;8(70):115164-115178 [PMID: 29383150]
  5. Clin Orthop Relat Res. 2001 Jun;(387):8-17 [PMID: 11400898]
  6. Free Radic Biol Med. 2018 Mar;117:76-89 [PMID: 29373843]
  7. J Nucl Cardiol. 2022 Oct;29(5):2404-2419 [PMID: 34476776]
  8. Front Pharmacol. 2022 Mar 16;13:841410 [PMID: 35370724]
  9. Angiology. 2005 Jul-Aug;56(4):403-7 [PMID: 16079923]
  10. Eur J Pharmacol. 2023 Apr 5;944:175584 [PMID: 36781043]
  11. Signal Transduct Target Ther. 2021 Feb 3;6(1):49 [PMID: 33536413]
  12. Biomed Res Int. 2021 Jan 19;2021:8880179 [PMID: 33532500]
  13. Mol Cancer Res. 2018 Jul;16(7):1073-1076 [PMID: 29592897]
  14. Free Radic Biol Med. 2019 Mar;133:162-168 [PMID: 29800655]
  15. Circulation. 2004 Nov 9;110(19):3055-61 [PMID: 15520304]
  16. Front Cell Dev Biol. 2022 Jan 10;9:779936 [PMID: 35083214]
  17. Signal Transduct Target Ther. 2024 Jan 8;9(1):12 [PMID: 38185705]
  18. Chem Biol. 2008 Mar;15(3):234-45 [PMID: 18355723]
  19. Signal Transduct Target Ther. 2022 Dec 16;7(1):391 [PMID: 36522308]
  20. FEBS Lett. 2005 Dec 19;579(30):6839-45 [PMID: 16325181]
  21. Am J Physiol Heart Circ Physiol. 2018 Mar 1;314(3):H659-H668 [PMID: 29127238]
  22. Cancer Cell. 2003 Mar;3(3):285-96 [PMID: 12676586]
  23. Cardiol Clin. 2001 Feb;19(1):91-112 [PMID: 11787816]
  24. Mol Psychiatry. 2021 Sep;26(9):4754-4769 [PMID: 32366950]
  25. Mol Med Rep. 2020 Feb;21(2):631-640 [PMID: 31974607]
  26. Biomed Pharmacother. 2022 Jan;145:112423 [PMID: 34800783]
  27. Cell Physiol Biochem. 2014;33(5):1293-303 [PMID: 24802592]
  28. Nitric Oxide. 2005 Mar;12(2):89-96 [PMID: 15740982]
  29. Cell Physiol Biochem. 2018;49(5):1734-1746 [PMID: 30248666]
  30. Am Heart J. 2015 Nov;170(5):971-80 [PMID: 26542507]
  31. DNA Cell Biol. 2020 Feb;39(2):210-225 [PMID: 31809190]
  32. Cardiovasc Ultrasound. 2017 Apr 12;15(1):11 [PMID: 28403861]
  33. Signal Transduct Target Ther. 2024 May 24;9(1):127 [PMID: 38782919]
  34. Exp Neurol. 2021 Nov;345:113828 [PMID: 34343528]
  35. Tohoku J Exp Med. 2008 Feb;214(2):151-8 [PMID: 18285673]
  36. Hum Cell. 2022 May;35(3):836-848 [PMID: 35212945]
  37. Nano Lett. 2017 Jan 11;17(1):284-291 [PMID: 28027643]
  38. Coron Artery Dis. 2018 Nov;29(7):579-586 [PMID: 29912782]
  39. Lancet. 1980 Dec 13;2(8207):1265-8 [PMID: 6108446]
  40. Front Pharmacol. 2021 Apr 14;12:628988 [PMID: 33935719]
  41. Front Cell Dev Biol. 2022 Jan 20;9:813668 [PMID: 35127725]
  42. N Engl J Med. 2007 Sep 13;357(11):1121-35 [PMID: 17855673]
  43. J Orthop Res. 2003 Nov;21(6):984-9 [PMID: 14554209]
  44. Nature. 2015 Apr 2;520(7545):57-62 [PMID: 25799988]
  45. Oxid Med Cell Longev. 2021 Oct 23;2021:9929687 [PMID: 34725566]
  46. Cell Res. 2019 Apr;29(4):263-264 [PMID: 30809018]
  47. Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2672-2680 [PMID: 30692261]
  48. N Engl J Med. 1986 Mar 27;314(13):818-22 [PMID: 3951514]
  49. J Am Coll Cardiol. 2020 Dec 22;76(25):2982-3021 [PMID: 33309175]
  50. Cell. 2012 May 25;149(5):1060-72 [PMID: 22632970]

MeSH Term

Ferroptosis
Myocytes, Cardiac
Rats
Animals
Apoptosis
Cell Hypoxia
Cell Line
Cell Survival
Reactive Oxygen Species
Oxygen
Extracorporeal Shockwave Therapy
Phospholipid Hydroperoxide Glutathione Peroxidase
Myocardial Reperfusion Injury
Mitochondria

Chemicals

Reactive Oxygen Species
Oxygen
Phospholipid Hydroperoxide Glutathione Peroxidase

Word Cloud

Created with Highcharts 10.0.0SWTcardiomyocyteprotectivelevelstherapymyocardialH/RferroptosisShockwaveischemiclow-energymechanismeffectcardiomyocyteshypoxia/reoxygenationcellinjurysignificantlydecreasingfunctionexpressionxCTinhibitingapoptosisnewalternativepatientsseverecoronaryarterydiseaseimprovessymptomsdeliveringshockstimulationischaemicmyocardiumpulsedwavesHoweverspecificfullyunderstoodespeciallyselectedratH9c2lineestablishstablemodelusedtherapeuticinterventionexploremechanismsresultsshowedincreasedviabilityGSHLDHROSMDAalsoimprovedmitochondrialmorphologycellsMeanwhilefoundincreaseGPX4Bcl-2Baxcleavedcaspase-3Moreoverreversedknockdownkeyregulatorproteinconclusionstudyshowscanattenuatehypoxia-reoxygenation-inducedprotectH/R-inducedmayimportantapplicationstreatmentclinicaldiseasesWaveTherapyAlleviatesHypoxia/Reoxygenation-InducedCardiomyocyteInjuryInhibitingApoptosisFerroptosis

Similar Articles

Cited By