INTRODUCTION: Platelets play a key role in coronary artery disease. They have the capacity of protein synthesis through translation of megakaryocyte-derived mRNAs, which may influence pathophysiological functions. The present study aimed to prove the concept that platelets from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) have differential mRNA expression profiles, in the hypothesis that this may influence their thrombogenicity. MATERIALS AND METHODS: Gene expression profiles were determined in RNA pools from resting platelets of patients with stable angina (SA, n = 14) or NSTE-ACS (n = 15) using a glass microarray platform. Validation was done by real-time PCR and immunoblot analyses in independent sets of individual samples (26 SA and 17 NSTE-ACS patients, in total). Parallel comparison with healthy subjects was performed to relate the relative abundance of validated genes in CAD patients to a control expression level. RESULTS: Microarray analysis identified 45 transcripts with a significant ≥ ± 2.0-fold difference in expression between NSTE-ACS and SA platelet pools. Thus, gene expression profiles at least partially discriminate unstable from stable CAD. Validation confirmed a significant over-expression of 3 genes in NSTE-ACS at both mRNA and protein level. In particular, the glycoprotein Ib β-polypeptide (GP1BB) was increased in NSTE-ACS also in comparison with healthy subjects. CONCLUSION: This study provides evidence that NSTE-ACS platelets are potentially preconditioned to a higher degree of reactivity on the transcriptional level. Our data suggest that a different composition of the mRNA pool might mediate an increased platelet prothrombotic potential in NSTE-ACS patients.
INTRODUCTION: Platelets play a key role in coronary artery disease. They have the capacity of protein synthesis through translation of megakaryocyte-derived mRNAs, which may influence pathophysiological functions. The present study aimed to prove the concept that platelets from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) have differential mRNA expression profiles, in the hypothesis that this may influence their thrombogenicity. MATERIALS AND METHODS: Gene expression profiles were determined in RNA pools from resting platelets of patients with stable angina (SA, n = 14) or NSTE-ACS (n = 15) using a glass microarray platform. Validation was done by real-time PCR and immunoblot analyses in independent sets of individual samples (26 SA and 17 NSTE-ACS patients, in total). Parallel comparison with healthy subjects was performed to relate the relative abundance of validated genes in CAD patients to a control expression level. RESULTS: Microarray analysis identified 45 transcripts with a significant ≥ ± 2.0-fold difference in expression between NSTE-ACS and SA platelet pools. Thus, gene expression profiles at least partially discriminate unstable from stable CAD. Validation confirmed a significant over-expression of 3 genes in NSTE-ACS at both mRNA and protein level. In particular, the glycoprotein Ib β-polypeptide (GP1BB) was increased in NSTE-ACS also in comparison with healthy subjects. CONCLUSION: This study provides evidence that NSTE-ACS platelets are potentially preconditioned to a higher degree of reactivity on the transcriptional level. Our data suggest that a different composition of the mRNA pool might mediate an increased platelet prothrombotic potential in NSTE-ACS patients.
Authors: Giovanni Cimmino; Loreta Pia Ciuffreda; Giovanni Ciccarelli; Paolo Calabrò; Fiorella Angelica Valeria Ferraiolo; Alessia Rivellino; Raffaele De Palma; Paolo Golino; Francesco Rossi; Plinio Cirillo; Liberato Berrino Journal: Front Cardiovasc Med Date: 2017-02-07