Platelet, CD40/CD40L, MPS-Cells: Partners in Crime

Abstract

Several suggestions showed a strong correlation of platelet and CD40/40L; CD40/40L is a member of TNF superfamily, the genes is located on chromosome X, and it is expressed on endothelial cells, SMC, fibroblast and activated platelet and plays a pivotal role in inflammatory and expression of adhesion molecules, and it stimulates the release of cytokines. It helps identifing patients with atherosclerosis and an increased risk of thrombosis, peripheral and cardiovascular disease (CAD and CHF). CD40/40L was measured by flow cytometry, and s-CD40L by ELISA. In platelet activation CD40L is translocated to the platelet surface and it is accompanied by the release of sCD40L and RONS (reactive ossigen and nitrogen species) and this contributes to atherothrombotic disease and inflammatory process by forming (CD40-40L/GPIIb-IIIa, CD40-40L/Pselectin- PSGL) complex strictly correlated with levels of ICAM-1 and VCAM-1, induced TF-expression and release of MMPs. Activated platelets release chemokines, enhance adhesion and aggregation cytochine like-factors and coagulation factors. Patients with thrombotic events had more platelet-monocyte aggregate (36.8 +/− 12.4 %) than controls (14.2 +/− 2.1 %) and sCD40L above 4.5 ng/l, ICAM-1 levels 248 +/− 10.8 ng/ml vs 168 +/− 5.4 ng/ml, VCAM-1 764 +/− 18.6 ng/ml vs 532 +/− 8.6 ng/ml. The interaction of platelet and MPS-cells were enhanced by activation of P-Selectin 38.6 +/− 12.4 ng/ml vs 20.4 +/− 4.4 ng/ml, and MCP-1 286 +/−10.4 pg/ ml vs 132 +/− 5.8 pg/ml which are one of the major promoter of inflammation. This finding demonstrated that the development and progression of atherosclerosis is critically dependent on these molecules; this may propose new therapeutic target for future therapies.