Background – Recent evidences from our group indicate that platelet-associated Tissue Factor (pTF) is increased and platelet transcriptome is modified in coronary artery disease (CAD) patients compared to healthy subjects. Type-2 diabetes mellitus (T2DM)-related metabolic unbalance enhances platelet reactivity. In this study we assessed whether T2DM affects pTF expression, platelet procoagulant phenotype, and transcriptome profile in CAD patients. Materials and methods - Thirty CAD patients with T2DM and 30 CAD patients without T2DM were enrolled. pTF was evaluated by flow cytometry on whole blood. The global haemostatic function was verified by using thromboelastometry (ROTEM). Platelet transcriptome profiles were evaluated using Illumina BeadChip Human HT-12 v4 microarrays. Results - T2DM patients showed significantly higher number of TF positive platelets compared to non-T2DM patients (3.7±1.2% and 2.4±0.5%, respectively). Moreover, the TF fold induction upon ADP stimulation was significantly higher in T2DM compared to non-T2DM patients (30.5±11.7% and 17.6±3.9%, respectively). Maximum Clot Firmness, Thrombodynamic Potential Index and Maximum Velocity of clot formation assessed with ROTEM were all significantly increased in diabetic patients. Microarray analysis showed that two molecular functions appeared significantly altered by T2DM in CAD patients, with 8 and 6 genes respectively upregulated: alternative splicing and nucleotide binding. Conclusions - The higher amount of TF positive platelet found in T2DM patients further extend our knowledge on the potential mechanism responsible for the T2DM-associated prothrombotic phenotype. The differentially expressed transcripts in T2DM platelets may provide insight into the mechanisms underlying the increased platelet reactivity and/or represent biomarkers for thrombotic risk.
|Titolo:||PLATELET PROTHROMBOTIC AND TRANSCRIPTOMIC PROFILE IN CAD PATIENTS WITH TYPE-2 DIABETES MELLITUS|
|Parole Chiave:||Haemoglobin; Post-storage leucodepletion; Washed red blood cells|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/11 - Malattie dell'Apparato Cardiovascolare
|Data di pubblicazione:||set-2012|
|Appare nelle tipologie:||01 - Articolo su periodico|