title: Mitogen-activated protein kinases activation in T lymphocytes of patients with acute coronary syndromes.
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.
authors.affiliation: Division of Cardiology, Laboratory of Molecular and Cellular Cardiology, University Magna Graecia, Viale Europa, Campus S. Venuta di Germaneto, Catanzaro, Italy. indolfi@unicz.it
authors.forename: Ciro
authors.initials: C
authors.lastname: Indolfi
authors.forename: Cosimo
authors.initials: C
authors.lastname: Gasparri
authors.forename: Carla
authors.initials: C
authors.lastname: Vicinanza
authors.forename: Daniela
authors.initials: D
authors.lastname: De Serio
authors.forename: Duino
authors.initials: D
authors.lastname: Boncompagni
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mongiardo
authors.forename: Carmen
authors.initials: C
authors.lastname: Spaccarotella
authors.forename: Valter
authors.initials: V
authors.lastname: Agosti
authors.forename: Daniele
authors.initials: D
authors.lastname: Torella
authors.forename: Antonio
authors.initials: A
authors.lastname: Curcio
mesh_terms: D054058:Acute Coronary Syndrome / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000175:diagnosis; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020928:Mitogen-Activated Protein Kinases