CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 AFRICA 35 Association between apelin-12 and creatine kinase-MB, depending on success of reperfusion in STEMI patients Xhevdet Krasniqi, Josip Vincelj, Masar Gashi, Blerim Berisha, Dardan Kocinaj Background: Acute myocardial infarction is characterised by an imbalance in the supply and demand of oxygen in the heart. It requires urgent reperfusion, and poor outcomes are attributed to myocardial ischaemia–reperfusion injury. We aimed to evaluate the association between apelin-12 levels and creatine kinase-MB activity in predicting the effectiveness of reperfusion therapy in ST-segment elevation myocardial infarction (STEMI) patients. Methods: In this study we included 72 patients with the following criteria: chest pain suggestive of myocardial ischaemia for at least 30 minutes, an electrocardiogram with ST-segment elevation (measured at the J-point) ≥ 2 mm in leads V2–V3 and/or ≥ 1 mm in the other leads, rise of specific biomarkers such as cardiac troponin and the MB fraction of creatine kinase (CK-MB), and those who underwent reperfusion therapy. Blood samples for the measurement of apelin-12 and creatine kinase-MB were collected 12 hours after the reperfusion therapy. Results: In patients with thrombolysis in myocardial infarction (TIMI) flow grade ≤ 2, the median of the apelin-12 level was 1.80 ng/ml (0.46–9.20), and with TIMI flow 3, it was 5.76 ng/ml (1.14–15.2). Variability was observed in the apelin values (Mann–Whitney test) based on TIMI flow grade (p < 0.001), while no variability was observed for creatine kinaseMB (p < 0.18). The degree of association between apelin-12 and creatine kinase-MB levels was analysed with Pearson’s correlation, enabling us to determine patients with successful reperfusion (determined as TIMI flow 3) (p < 0.004), and those with unsuccessful reperfusion (with TIMI flow ≤ 2) (p = 0.86). Conclusion: In STEMI patients undergoing reperfusion therapy, apelin-12 level was associated with creatine kinase-MB activity according to the success of the reperfusion. Keywords: apelin, myocardial infarction, reperfusion Submitted 13/9/20, accepted 16/12/22 Published online 5/5/23 Cardiovasc J Afr 2024; 35: 35–29 www.cvja.co.za DOI: 10.5830/CVJA-2023-002 Myocardial ischaemia results from an imbalance between the oxygen supply and demand in the heart preceding the development of myocardial infarction.1 It is known that in cardiomyocytes, creatine kinase (CK) appears as three isoenzymes: creatine kinase M-type, creatine kinase B-type and mitochondrial sarcomere creatine kinase.2 On the other hand, adenosine triphosphate (ATP) as a primary carrier of energy in cardiac cells is produced from a variety of substrates (fatty acids and glucose) generally in the mitochondria through oxidative phosphorylation. The creatine kinase M-type (CKM) coupled to ATPase regenerates ATP according to the actual energy requirements.3 The high-energy phosphoryl bonds of ATP are available at the sites of utilisation and require a phosphagen system that consists of a reversible interaction of creatine and ATP under the control of cytosolic CKM: Creatine + ATP ↔ phosphocreatine + ADP + H+.4,5 In myocardial infarction, the levels of ATP and phosphocreatine are rapidly depleted due to lack of oxygen, resulting in tissue damage and elevating the levels of the MB fraction of creatine kinase (CK-MB).6 During hypoxia, apelin gene expression and secretion are increased through the activation of hypoxia-inducible factor.7-9 The apelin gene (located on the human X chromosome) encodes a 77-amino acid preproprotein (prepro-apelin) that is cleaved by endopeptidases into a biologically active peptide such as apelin-12. This is followed by positive effects on the cardiovascular system.7,10-15 After the binding of apelin with angiotensin receptor like1 (APJ), phospholipase C is activated, generating inositol trisphosphate and diacylglycerol from phosphatidyl inositol bisphosphate. Furthermore, diacylglycerol activates protein kinase C through which apelin activates its sites on troponin I, thereby regulating ATPase activity in the myocardium influenced by CK (Fig. 1).16-19 Acute myocardial infarction due to occlusion of the coronary artery is characterised by an imbalance between the heart’s oxygen demand and supply, which requires urgent reperfusion to rescue the ischaemic myocardium from expected death. Poor outcomes are attributed to myocardial ischaemia–reperfusion injury, which is largely mediated by the cytotoxic effects of free radicals generated during ischaemia, complement activation, injury of endothelial cells and inflammation.20-25 Apelin activates components of the reperfusion injury salvage kinase pathway, such as phosphatidylinositol-3-OH kinase, Akt/protein kinase B and p44/42 mitogen-activated protein Clinical Hospital Dubrava, Zagreb and Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia Josip Vincelj, MD, PhD Faculty of Medicine, University of Prishtina Hasan Prishtina, Kosovo Xhevdet Krasniqi, MD Masar Gashi, MD, PhD University Clinical Centre of Kosovo, Kosovo Xhevdet Krasniqi, MD Masar Gashi, MD, PhD Blerim Berisha, MD Faculty of Medicine, University of Gjakova Fehmi Agani, Kosovo Dardan Kocinaj, MD, PhD, dardankocinaj@gmail.com
RkJQdWJsaXNoZXIy NDIzNzc=