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Correlation of plasma cardiac troponin and frequency of perforin expressing lymphocytes in peripheral blood of patients with myocardial infarction

Introduction: Myocardial infarctions with ST segment elevation (STEMI) and without ST segment elevation (NSTEMI) appear on the basis of the critical stenosis of coronary artery. Emergency percutaneous coronary intervention with stent implantation is the preferred treatment for STEMI patients, whereas the majority of NSTEMI patients are conservatively treated by standard drug therapy. In both groups of patients, strong inflammatory process activates leukocytes in the blood stream and recruits them into the vessel wall. These cells are able to trigger vascular smooth muscle cell death, due to the expression of perforin (P). P is potentially dangerous, primary inflammatory and cytotoxic mediator, stored in cytoplasmic granules of the immune effectors. The possible contribution of P to the development of cardiac injury, as a consequence of strong cell- mediated immune response in patients with acute MI, is still largely unknown. The aim of this investigation was to compare P expression in peripheral blood lymphocyte subpopulations in STEMI and NSTEMI patients within the first week after the myocardial infarction and correlate percentage of P expressing lymphocytes with plasma concentration of cardiac troponin I (cTnI), as a biomarker of myocardial tissue necrosis. Material and methods: We enrolled 15 patients with NSTEMI in this study (age, 60 years ; 51.5/71 (median, 25th/75th percentiles) and sex and age matched 15 STEMI patients, 12 healthy controls, as well as 8 patients that receive  blocker in the therapy of hypertension. The simultaneous detection of intracellular P and cell surface CD3 and CD56 molecules was performed with flow cytometry. CD3/complement component 9 (CC9) and CD56/CC9 cells were visualized in myocardial paraffin- embedded tissue sections from persons who died in the first or in the fifth week after myocardial infarction and from patients who died from non-cardiac causes by double labeling using immunohistology. Results: The percentage of total peripheral blood P+ lymphocytes was elevated due to the increased frequency of P+ cells within NK subsets, T and NKT cells in patients on days 1, 4 and/or 7 after NSTEMI when compared to healthy controls and/or  blocker. Positive correlations were found between cTnI plasma concentrations and the frequency of P+ cells, P+ T cells on day 1, P+ NK cells and their CD56+dim and CD56+bright subsets on day 4 and P+CD56+bright subset on day 7 after the NSTEMI. In STEMI patients the frequency of P+ lymphocytes and P+ cells within lymphocyte subpopulations did not significantly change and negative correlations was found between cTnI plasma concentrations and the frequency of P+ lymphocytes, P+ T cells and P+ NK cells on day 4, and the frequency of P+ cells, P+ NK cells on day 7. CD56+ and CD3+ lymphocytes were found near the necrotic cardiomyocytes suggesting their tissue recruitment. Conclusion: NSTEMI patients treated with medicaments have a strong and prolonged P-mediated systemic inflammatory reaction, when compared to STEMI patients after the percutaneous coronary interventions, although the myocardial recruitment of T and NK cells in both group of patients might sustain auto-aggressive reactions towards myocardial tissue during the development of myocardial infarction.

lymphocyte ; myocardial infarction ; perforin ; peripheral blood ; troponin I

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