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Mitogen-activated protein kinases activation in T lymphocytes of patients with acute coronary syndromes

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Abstract

Current available biomarkers cannot identify myocardial ischemia without necrosis. To overcome this issue and to increase diagnostic power, we evaluated the activation of the three MAPK pathways, ERK1/2, JNK and p38, in T lymphocytes of patients with acute coronary syndromes (ACS). We included sixty consecutive patients affected by either unstable angina (UA, N = 22), Non- ST-segment elevation MI (NSTEMI, N = 19) or ST-segment elevation MI (STEMI, N = 19). Two separate groups of patients were matched as controls: healthy subjects (CTRL, N = 20) and patients with stable coronary artery disease (CAD, N = 21). MAPK activation in T lymphocytes, measured by phospho-ERK1/2, phospho-JNK and phospho-p38 levels, was assessed by flow cytometry analysis which revealed significantly increased phosphorylated levels of ERK1/2 in patients with UA, compared to controls. In UA patients no significant changes were detected for phospho-JNK compared to both control groups. NSTEMI and STEMI groups showed a statistically significant increase in both phospho-ERK1/2 and phospho-JNK, compared to control groups. All ACS groups demonstrated significantly increased phosphorylation of p38 compared to CTRL, but not CAD. ROC curves showed that a cut-off value of 22.5 intensity of fluorescence for phospho-ERK1/2 was able to significantly discriminate UA patients from patients with stable angina with 78% sensitivity and 90% specificity. Therefore, a differential MAPK activation in T lymphocytes denotes patients with ACS. Indeed, patients with unstable angina are identified with high specificity by activated ERK1/2 and normal JNK levels. These data could represent a valuable new molecular signature to be used as specific biomarkers for the diagnosis of unstable angina within ACS.

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Acknowledgments

This study was supported, in part, by Grants for Scientific Research from the Ministry of the Education, University and Research of Italy (PRIN2003065977_002, RBAU018WWP_001), by Ricerca sanitaria finalizzata 2007—Programma Strategico APICE “Activity of Platelets after Inhibition and Cardiovascular Events”, and by GENECOR, a non-profit organization.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Cardiology, Laboratory of Molecular and Cellular Cardiology, University Magna Graecia, Viale Europa, Campus “S. Venuta” di Germaneto, 88100, Catanzaro, Italy

    Ciro Indolfi, Cosimo Gasparri, Carla Vicinanza, Daniela De Serio, Duino Boncompagni, Annalisa Mongiardo, Carmen Spaccarotella, Daniele Torella & Antonio Curcio

  2. Department of Experimental and Clinical Medicine, Laboratory of Molecular Oncology, University Magna Graecia, Viale Europa, Campus “S. Venuta” di Germaneto, 88100, Catanzaro, Italy

    Valter Agosti

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  1. Ciro Indolfi
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Correspondence to Ciro Indolfi.

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Indolfi, C., Gasparri, C., Vicinanza, C. et al. Mitogen-activated protein kinases activation in T lymphocytes of patients with acute coronary syndromes. Basic Res Cardiol 106, 667–679 (2011). https://doi.org/10.1007/s00395-011-0172-1

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