PLATELET ACTIVATION AND ASSOCIATED TRANSCRIPTIONAL SIGNATURE IN TYPE 2 DIABETIC PATIENTS WITH STABLE CORONARY ARTERY DISEASE: INSIGHTS INTO THEIR THROMBOTIC PROPENSITY.

Platelet activation and associated transcriptional signature in type 2 diabetic patients with stable coronary artery disease: insights into their thrombotic propensity Several studies indicate that despite aspirin therapy patients with type-2 diabetes mellitus (T2DM) have both an enhanced platelet reactivity and a hypercoagulable state, supporting the evidence of a greater incidence of coronary artery disease (CAD) compared to patients without T2DM. Tissue Factor (TF) is the principal activator of blood coagulation; it is also expressed by platelets, which, upon activation translocate the protein on the cell surface. We have previously shown that platelet-associated TF (pTF) is increased in CAD patients compared to healthy subjects contributing to an increased thrombin generation capacity. No information is still available on pTF expression in diabetic patients with stable angina (SA). Our aim is to provide insight into the enhanced risk of thrombotic complications associated with T2DM in order to clarify pathways altered by diabetes and to find new potential targets of pharmacological modulation. In this study we assessed whether T2DM affects pTF expression, the overall prothrombotic potential and platelet transcriptome profile in patients with SA. We enrolled 85 patients with stable angina (SA), 32 with T2DM and 53 without T2DM; 28 diabetic patients without SA and 37 healthy subjects (HS). Assessment of surface and intracytoplasmic pTF expression was performed by whole blood flow cytometry. The prothrombotic potential was analyzed by thrombin generation assay both in plasma and in isolated platelets using Thrombinoscope. The global haemostatic function was evaluated by thromboelastometry (Rotem). Platelet transcriptome profiles were studied using Illumina BeadChip Human HT-12 v4 microarray. Haematologic parameters were comparable among the 4 groups except for the percentage of immature platelet fraction, which was higher in SA patients with T2DM (p<0.05). T2DM was associated with an increase in TF expression on platelet surface: it was significantly increased in SA patients with T2DM compared to SA without T2DM and HS (p<0.05). Moreover a significantly higher number of intracytoplasmic TF+-platelets was found in SA patients with T2DM compared to patients without T2DM (27.53\ub12.8 vs. 14.98\ub11,34, p