CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 38 AFRICA sarcoplasmic reticulum membranes and is capable of linking energy production and utilisation, using phosphocreatine to rephosphorylate all of the ADP produced by the ATPases.30 One of the enzymes that is activated after the binding of apelin to its receptor is protein kinase C, through which apelin activates its sites on troponin I, thereby regulating Ca2+ sensitivity and ATPase activity in the myocardium.18,19 Therefore, in patients with successful reperfusion (TIMI flow 3), the expression of hypoxia-inducible factor 1-alpha (HIF-1α) increased the level of apelin, which regulated ATPase activity and was associated with increased levels of CK-MB. In our study, the subgroup with unsuccessful reperfusion exhibited a decreased level of apelin-12 that did not correlate with the level of CK-MB. Reperfusion therapy may induce pathological events in patients with acute myocardial infarction, leading to myocardial tissue injury. Increased generation of highly reactive oxygen species in the heart within minutes of reperfusion has been followed by decreased stability of HIF-1α.31,32 In patients with unsuccessful reperfusion (TIMI flow ≤ 2), decreased stability of HIF-1α is followed by decreasing levels of apelin-12 and its association with CK-MB. Presumably, the apelin/APJ axis may serve as a potential target for the prevention of myocardial reperfusion injury in patients with STEMI. One limitation is that this observational study had a relatively limited number of patients. Conclusion In STEMI patients undergoing reperfusion therapy, apelin-12 levels were associated with CK-MB activity according to the success of reperfusion. This indicates the role of apelin-12 in the CK system. In the future, apelin-12 could be used as a cardioprotective agent. We are grateful to the patients who participated in this study. References 1. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD. Executive group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Circulation 2018; 138(20): e618–3651. 2. Waskova-Arnostova P, Kasparova D, Elsnicova B, Novotny J, Neckar J, Kolar F, et al. Chronic hypoxia enhances expression and activity of mitochondrial creatine kinase and hexokinase in the rat ventricular myocardium. Cell Physiol Biochem 2014; 33: 310–320. 3. Zurmanova J, Difato F, Malacova D, Mejsnar J, Stefl B and Zahradnik I. Creatine kinase binds more firmly to the M-band of rabbit skeletal muscle myofibrils in the presence of its substrates. Mol Cell Biochem 2007; 305: 55–61. 4. Neubauer S. The failing heart – an engine out of fuel. N Engl J Med 2007; 356: 1140–1151. 5. Wyss M and Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev 2000: 80: 1107–1213. 6. Ten Hove M, Lygate CA, Fischer A, Schneider JE, Sang AE, Hulbert K, et al. Reduced inotropic reserve and increased susceptibility to cardiac ischemia/reperfusion injury in phosphocreatine-deficient guanidinoacetate-N methyltransferase-knockout mice. Circulation 2005; 111: 2477–2485. 7. Ronkainen VP, Ronkainen JJ, Hanninen SL, Leskinen H, Ruas JL, Pereira T, et al. Hypoxia inducible factor regulates the cardiac expression and secretion of apelin. FASEB J 2007; 21(8): 1821–1830. 8. Jianqiang P, Ping Z, Xinmin F, Zhenhua Y, Ming Z, Ying G. Expression of hypoxia-inducible factor 1 alpha ameliorate myocardial ischemia in rat. Biochem Biophys Res Commun 2015; 465(4): 691–695. 9. Cheng C, Li P, Wang YG, Bi MH, Wu PS. Study on the expression of VEGF and HIF-1α in infarct area of rats with AMI. Eur Rev Med Pharmacol Sci 2016; 20(1): 115–119. 10. Japp A, Newby D. The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential. Biochem Pharmacol 2008; 75: 1882–1892. 11. Chandrasekaran B, Dar O, McDonagh T. The role of apelin in cardiovascular function and heart failure. Eur J Heart Fail 2008; 10: 725–732. 12. O’Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, et al. A human gene that shows identity with the gene encoding the angiotension receptor is located on chromosome 11. Gene 1993; 136: 355–360. 13. Szokodi I, Tavi P, Földes G, Voutilainen-Myllylä S, Ilves M, Tokola H, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res 2002; 91: 434–440. 14. Neves SR, Ram PT, Lyengar R. G protein pathways. Science 2002; 296: 1636–1639. 15. Karmazyn M, Gan XT, Humphreys RA, Yoshida H, Kusumoto K. The myocardial Na(+)-H(+) exchange: structure, regulation, and its role in heart disease. Cir Res 1999; 85: 777–786. 16. Yamamura K, Steenbergen C, Murphy E. Protein kinase C and preconditioning: role of sarcoplasmic reticulum. Am J Physiol Heart Circ Pysiol 2005; 289: 2484–2490. 17. Wang C, Du JF, Wu F, Wang HC. Apelin decreases the SR Ca 2+ content but enhances the amplitude of [Ca2+]i transient and contractions during twitches in isolated rat cardiac myocytes. Am J Physiol Heart Circ Physiol 2008; 294: 2540–2546. 18. Farkasfalvi K, Stagg M, Coppen S, Siedlecka U, Lee J, Soppa GK, et al. Direct effects of apelin on cardiomyocyte contractility and electrophysiology. Biochem Biophys Res Commun 2007; 357: 889–895. 19. Pi YQ, Zhang D, Kemnitz KR, Wang H, Walker JW. Protein kinase C and A sites on troponin I regulate myofilament Ca2+, sensitivity and ATPase activity in the mouse myocardium. J Physiol 2003; 552: 845–857. 20. Liem DA, Honda HM, Zhang J, Woo D, Ping P. Past and present course of cardioprotection against ischemia–reperfusion injury. J Appl Physiol 2007; 103: 2129–2136. 21. Braunwald E, Kloner RA. Myocardial reperfusion: A double-edged sword? J Clin Invest 1985; 76: 1713–1719. 22. Zaugg M, Lou PH, Lucchinetti E, Gandhi M, Clanachan AS. Postconditioning with Intralipid emulsion protects against reperfusion injury in post-infarct remodeled rat hearts by activation of ROS-Akt/ Erk signaling. Transl Res 2017; 186: 36–51.e2. 23. Turer AT, Hill JA. Pathogenesis of myocardial ischemia–reperfusion injury and rationale for therapy. Am J Cardiol 2010; 106: 360–368. 24. Luo Y, Pan YZ, Zeng C, Li GL, Lei XM, Liu Z, et al. Altered serum creatine kinase level and cardiac function in ischemia reperfusion injury during percutaneous coronary intervention. Med Sci Monit 2011; 17: 474–479. 25. Cannon RO 3rd. Mechanisms, management and future directions for reperfusion injury after acute myocardial infarction. Nat Clin Pract Cardiovasc Med 2005; 2: 88–94. 26. Simpkin JC, Yellon DM, Davidson SM, Lim SY, Wynne AM, Smith CC. Apelin-13 and apelin-36 exhibit direct cardioprotective activity against
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