ABC | Volume 113, Nº1, July 2019

Original Article Kızıltunç et al. Sirtuins in acute myocardial infarction patients Arq Bras Cardiol. 2019; 113(1):33-39 Table 3 – Correlation analysis of prognostic variables of AMI patients with sirtuins Baseline Sirtuin 1 Baseline Sirtuin 3 Baseline Sirtuin 6 TIMI Score (Spearman’s Rho/p) 0.109/0.508 -0.093/0.574 0.015/0.930 GRACE Score (Spearman’s Rho/ p) In hospital mortality -0.003/0.983 -0.478/0.002 -0.115/0.486 6. month mortality -0.001/0.997 -0.351/0.028 -0.137/0.406 In hospital MI/mortality 0.045/0.785 -0.509/0.001 0.041/0.805 6. month MI/mortality 0.021/0.901 -0.501/0.001 -0.016/0.922 proBNP, (Spearman’s Rho/ p) 0.294/0.073 -0.137/0.412 0.108/0.517 Peak Troponin T (Spearman’s Rho/ p) -0.107/0.518 -0.259/0.111 0.012/0.942 Time to Perfusion (Spearman’s Rho/ p) 0.331/0.037 -0.249/0.121 0.312/0.050 CRP, (Spearman’s Rho/ p) 0.312/0.053 -0.029/0.862 0.357/0.026 EF, (Spearman’s Rho/ p) -0.009/0.956 0.150/0.356 -0.132/0.419 AMI: acute myocardial infarction; BNP: brain natriuretic peptide; CRP: c reactive protein; EF: ejection fraction; TIMI: thrombolysis in myocardial infarction. Our findings regarding the association between sirtuins and the parameters reflecting infarction size like peak troponin, ejection fraction and pro BNP levels were also remarkable. Opening the occluded artery and restoring the blood flow to the myocardium is the mainstay of the AMI management. However, it was suggested that restoration of blood flow may account for further myocardial damage and it is termed as reperfusion injury. 33 Microvascular obstruction, myocyte hypercontracture and contraction band necrosis, free radical generation and inflammatory cell accumulation are the proposed mechanisms for reperfusion injury. 34 Ischemic preconditioning, which reduces reperfusion injury can be defined as transient, sublethal ischemic episodes rendering the myocardium more resistant to a sustained, lethal ischemic period. Since first described by Murry et al., 35 ischemic preconditioning has become the most relevant entity against reperfusion injury. Ischemic preconditioning requires complex intracellular molecular interactions and the molecular mechanism is still unclear. 36 It is suggested that some sirtuin types reduces ischemia reperfusion injury. In an experimental study, inhibition of sirtuin 1 resulted in reduction of bakuchiol induced cardioprotection in rat hearts. 37 Opening of the mitochondrial permeability transposition pores are crucial in the pathophysiology of ischemia reperfusion injury. Sirtuin 3 deacetylates the regulatory component of the mitochondrial permeability transposition pore and sirtuin 3 deficient mice myocytes exhibited an increase in mitochondrial swelling due to increase in the number of opened mitochondrial permeability transposition pores. 38 In this study, we investigated whether there was any association between serum sirtuin levels and infarct size markers. There was no correlation between serum sirtuin levels and peak troponin levels, LVEF and pro BNP levels in AMI patients. These findings reflect that serum sirtuin 1, 3 and 6 levels were not associated with the infarct size. Pre infarction angina pectoris can be used as the surrogate marker of ischemic preconditioning in daily practice and is associated with reduced peak troponin levels in AMI patients. 39 Although the number of subjects were low to make a firm conclusion, no difference was evident about serum sirtuin 1, 3 and 6 levels in the patients with and without pre infarction angina. Finally, we should mention about the association between serum sirtuin 3 levels and GRACE score, and between reperfusion duration and serum sirtuin 1/6 levels. GRACE score is a well-known and validated risk score for morbidity and mortality in AMI patients. 16 Although we could not find any correlation between serum sirtuin 3 levels and prognostic markers like peak troponin, pro-BNP and LVEF, the negative correlation between serum sirtuin 3 levels and GRACE score may be an inspiration for further studies to investigate the role of serum sirtuin 3 levels for the risk assessment in AMI patients. We found a positive correlation between serum sirtuin 1/sirtuin 6 levels and reperfusion duration. The duration between symptom onset and reperfusion was not a marker of mortality in STEMI patients. 40 Although correlated with reperfusion duration positively, sirtuin 1 and sirtuin 6 levels were not correlated with prognostic markers in AMI patients. There are some limitations of our study. The small sample size seems the most important limitation of the study. The other important limitation is the methodological differences with previous studies. In previous studies, sirtuin analysis was performed with specimens from atherosclerotic plaques or peripheral mononuclear cells. Sirtuin mRNA levels and protein expression levels were evaluated in those studies. In our study, we directlymeasured serumsirtuin levels. Although our methodology was not the same with other studies, we firstly investigated serum sirtuin levels in our particular study population. This can be accepted as the originality of our study. Conclusion Serum sirtuin 1, sirtuin 3 and sirtuin 6 levels did not significantly differ between AMI patients and patients with normal coronary arteries. No temporal change was found in the serum levels of these sirtuins in the AMI course and there was no correlation between the serum levels of these sirtuins and the parameters reflecting myocardial infarct size like peak troponin level, LVEF and pro-BNP. We detected a negative correlation between sirtuin 3 and GRACE score, as a secondary finding. Cardioprotective role of serum sirtuin 1, 3 and 6 needs more investigation in AMI patients. 37