|Institution:||Università degli Studi di Milano|
|Keywords:||platelet; coronary artery disease; chronic kidney disease; Settore BIO/14 - Farmacologia|
|Full text PDF:||http://hdl.handle.net/2434/354143|
BACKGROUND - Patients with CKD present a higher incidence of coronary artery disease (CAD) and increasing evidence indicates that these patients are more likely to die of cardiovascular disease than to develop kidney failure. CKD patients show a double haemostatic profile: thrombotic tendencies, but also a bleeding diathesis. Platelets and Tissue Factor (TF), the main activator of blood coagulation, play a key role in the pathogenesis and in the thrombotic complications of CAD. TF is expressed also by circulating platelets and, of interest, platelet-associated TF expression is higher in acute coronary syndrome (ACS) patients. However, there are no studies focused on platelet-associated TF expression in CAD patients with CKD. Moreover, although it is reported that platelet transcriptome may vary in pathological conditions, no information is still available on the changes that may occur in platelet transcriptome of CAD patients with CKD. Finally, patients with end-stage renal disease (ESRD) present changes in the expression of plasma proteins associated to atherosclerosis, but no data are so far available on the plasma proteomic profile of CAD patients with mild-to-moderate CKD. AIM - The aim of this project has been to further characterize the haemostatic tendencies (assessment of TF expression and of the global haemostatic function of whole blood), the platelet transcriptome and the plasma proteome of CAD patients with and without CKD. METHODS - 139 ACS patients with (n=31) and without CKD (n=108) and 217 SA patients with (n=49) and without CKD (n=168) were enrolled. The glomerular filtration rate (GFR) has been calculated with the MDRD CKD EPI Equation and CKD is defined by an estimated GFR value < 60 ml/min. Assessment of surface and intracellular platelet TF expression has been performed by whole blood flow cytometry; the global haemostatic function by thromboelastometry (ROTEM); platelet transcriptome profiles using Illumina BeadChip Human HT-12 v4 microarray; the plasma proteomic profile by the classical gel-based proteomic approach and the results confirmed by ELISA analysis. RESULTS - The percentage of TF expression on platelet surface is significantly lower in CKD patients compared to patients without CKD in resting condition (ACS: 4.07%±1.05 and 5.23%±0.82 respectively, p<0,05; SA: 1.96%±0.8 versus 2.72%±0.41, respectively, p<0,05) and this trend is also observed after ADP stimulation (ACS: 20.32%±2.58 and 21.71%±1.52 respectively, p>0,05; SA: 12.93%±2.73 and 16.54%±1.52 respectively, p>0.05). This result is also supported by the intracellular expression of platelet TF performed on a subgroup of ACS patients: intracellular TF is significantly lower in patients with CKD compared to those without CKD (19.49%±4.04 and 27.53%±5.16 respectively, p<0,001). The haemostatic function of blood, assessed by thromboelastometry, shows that, in physiological conditions, the presence of CKD exerts different effects on the global haemostatic potential in SA and ACS patients, but in the presence of a platelet… Advisors/Committee Members: tutor, M. Camera, coordinatore: A. Corsini, CAMERA, MARINA, CORSINI, ALBERTO.