The role of protein kinase C and PI3-kinase in the mechanism of the cardioprotective effect of remote ischemic postconditioning
https://doi.org/10.20538/1682-0363-2021-4-6-10
Abstract
Background. Acute myocardial infarction (AMI) with ST segment elevation is associated with high incidence of complications. Mortality from AMI is about 5%, which has not decreased in recent years. Revascularization provides recovery of coronary blood flow, but also contributes to the occurrence of reperfusion injury to the heart. Remote ischemic postconditioning (RIPostC) is a promising, non-invasive method that can effectively and safely reduce the infarct size.
The aim of the study was to investigate the role of protein kinase C and PI3-kinase in the development of the infarct-limiting effect of remote ischemic postconditioning.
Materials and methods. The study was performed on Wistar rats. Coronary artery occlusion (45 min) and reperfusion (2 h) were performed. The infarct size (IS) and the size of area at risk (AAR) were assessed. RIPostC was modeled by applying tourniquets to the hind limbs in the hip joint immediately after the restoration of coronary blood flow. All inhibitors were administered intravenously 10 min before reperfusion.
Results. In the control group, the IS / AAR ratio was 44%. RIPostC reduced the IS / AAR ratio by about 50%. Preliminary administration of the protein kinase C inhibitor chelerythrine and the PI3-kinase inhibitor wortmannin eliminated the cardioprotective effect of RIPostC.
Conclusion. The mechanism of the infarct-limiting effect of RIPostC is implemented through activation of protein kinase C and PI3-kinase.
About the Authors
A. V. Mukhomedzyanov
Cardiology Research Institute, Tomsk National Research Medical Center (NRMC), Russian Academy of Sciences
Russian Federation
Russian Federation
111а, Kievskaya Str., Tomsk, 634012
N. V. Naryzhnaya
Cardiology Research Institute, Tomsk National Research Medical Center (NRMC), Russian Academy of Sciences
Russian Federation
Russian Federation
111а, Kievskaya Str., Tomsk, 634012
L. N. Maslov
Cardiology Research Institute, Tomsk National Research Medical Center (NRMC), Russian Academy of Sciences
Russian Federation
Russian Federation
111а, Kievskaya Str., Tomsk, 634012
References
1. Vaidya S.R., Devarapally S.R., Arora S. Infarct related artery only versus complete revascularization in ST-segment elevation myocardial infarction and multi vessel disease: a meta-analysis. Cardiovasc. Diagn. Ther. 2017; 7 (1): 16–26. DOI: 10.21037/cdt.2016.08.06.
2. Zhou Y., Chen S., Zhu X., Gui J., Abusaada K. Prior beta blockers use is independently associated with increased in patient mortality in patients presenting with acute myocardial infarction. Int. J. Cardiol. 2017; 243: 81–85. DOI: 10.1016/j.ijcard.2017.03.004.
3. McCartney P.J., Berry C. Redefining successful primary PCI. Eur. Heart J. Cardiovasc. Imaging. 2019; 20 (2): 133–135. DOI: 10.1093/ehjci/jey159.
4. Ndrepepa G. Improving myocardial injury, infarct size, and myocardial salvage in the era of primary PCI for STEMI. Coron. Artery Dis. 2015; 26 (4): 341–355. DOI: 10.1097/mca.0000000000000220.
5. Маслов Л.Н., Барбараш О.Л. Фармакологические подходы к ограничению размера инфаркта миокарда у пациентов с острым инфарктом миокарда. Экспериментальная и клиническая фармакология. 2018; 81 (3): 75–82. DOI: 10.30906/0869-2092-2018-81-3-34-41.
6. Kerendi F., Kin H., Halkos M.E., Jiang R., Zatta A.J., Zhao Z.Q., Guyton R.A., Vinten-Johansen J. Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res. Cardiol. 2005; 100 (5): 404–412. DOI: 10.1007/s00395-005-0539-2.
7. Heusch G. Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ. Res. 2015; 116 (4): 674–699. DOI: 10.1161/circresaha.116.305348.
8. Maslov L.N., Naryzhnaya N.V., Tsibulnikov S.Yu., Kolar F., Zhang Y., Wang H., Gusakova A.M., Lishmanov Yu.B. Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia. Life Sci. 2013; 93 (9–11): 373–379. DOI: 10.1016/j.lfs.2013.07.018.
9. Maslov L.N., Lishmanov Yu.B., Oeltgen P.R., Barzakh E.I., Krylatov A.V., Govindaswami M., Brown S.A. Activation of peripheral δ2 opioid receptors increases cardiac tolerance to ischemia/reperfusion injury: Involvement of protein kinase C, NO-synthase, KATP channels and the autonomic nervous system. Life Sci. 2009; 84 (19–20): 657–663. DOI: 10.1016/j.lfs.2009.02.016.
10. Fettiplace M.R., Kowal K., Ripper R., Young A., Lis K., Rubinstein I., Bonini M., Minshall R., Weinberg G. Insulin signaling in bupivacaine-induced cardiac toxicity: sensitization during recovery and potentiation by lipid emulsion. Anesthesiology. 2016; 124 (2): 428–442. DOI: 10.1097/aln.0000000000000974.
11. Cohen M.V., Downey J.M. Signalling pathways and mechanisms of protection in pre- and postconditioning: historical perspective and lessons for the future. Br. J. Pharmacol. 2015; 172 (8): 1913–3192. DOI: 10.1111/bph.12903.
12. Hausenloy D.J., Yellon D.M. Ischaemic conditioning and reperfusion injury. Nat. Rev. Cardiol. 2016; 13 (4): 193–209. DOI: 10.1038/nrcardio.2016.5.
13. Breivik L., Helgeland E., Aarnes E.K., Mrdalj J., Jonassen A.K. Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/ Akt-dependent cell-survival signaling at reperfusion. Basic Res. Cardiol. 2011; 106 (1): 135–145. DOI: 10.1007/s00395-010-0133-0.
14. Liang D., He X.B., Wang Z., Li C., Gao B.Y., Wu J.F., Bai Y.L. Remote limb ischemic postconditioning promotes motor function recovery in a rat model of ischemic stroke via the up-regulation of endogenous tissue kallikrein. CNS Neurosci. Ther. 2018; 24 (6): 519–527. DOI: 10.1111/cns.12813.
Review
For citations:
Mukhomedzyanov A.V., Naryzhnaya N.V., Maslov L.N. The role of protein kinase C and PI3-kinase in the mechanism of the cardioprotective effect of remote ischemic postconditioning. Bulletin of Siberian Medicine. 2021;20(4):6-10. https://doi.org/10.20538/1682-0363-2021-4-6-10
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