The role of platelets in diabetic nephropathy and renal fibrosis

Diabetic nephropathy is accompanied by high platelet (re)activity leading to increased risk for cardiovascular disease. Besides their role in hemostasis, platelets are active players in inflammation and fibrosis as well. This thesis aimed to elucidate the role of platelets in diabetic nephropathy and renal fibrosis. First, the most effective model for inducing experimental diabetic nephropathy in mice was examined. This model, comprising unilateral nephrectomy followed by streptozotocin injections, was used to study the effect of platelet inhibition by ticagrelor in diabetic nephropathy in mice. We found that ticagrelor is protective against the development of diabetic nephropathy, most likely by protection to the renal endothelium. Furthermore, we found that thrombocytopenia affects macrophage infiltration in obstruction-induced renal fibrosis. The fourth study revealed that diabetic patients with different stages of diabetic nephropathy display distinct profiles of plasma extracellular vesicles, regarding both the cellular origin and the microRNA content. In the final chapter of the thesis, PBS-citrate buffer was compared with PBS-citrate + ACD (acid citrate dextrose) buffer, in order to optimize the simultaneous isolation of platelets and platelet-derived extracellular vesicles by size-exclusion chromatography. The addition of ACD was found to be crucial to prevent ex vivo platelet activation and loss of platelet extracellular vesicles.