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Fig. 3 | BMC Medicine

Fig. 3

From: Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments

Fig. 3

The damaging effects of activated platelets on endothelial cell function and activation. Activated platelets release large quantities of PICs, ROS and chemokines such as CD40, RANTES and PF4. PICS and CD40 can engage their cognate receptors on the surface of ECs activating downstream signalling pathways culminating in the activation of NF-κB. PF4 and RANTES may also engage with the surface of ECs, thereby summoning leucocytes and stimulating their differentiation and activation via a range of mechanisms ultimately also resulting in EC NF-κB activation. In addition, high levels of circulating hydrogen peroxide, produced by the activity of platelets, neutrophils and allopurinol, may directly enter ECs via aquaporin receptors. Such influx results in the activation of hydrogen peroxide production by NOX enzymes and mitochondria ultimately acting as another vehicle driving NF-κB upregulation. The subsequent upregulation of NO, PICs and ROS also compromises mitochondrial ATP production while the NF-κB-mediated downregulation of SIRT-1, PGC-1α and PPAR-γ inhibit mitochondrial biogenesis and disrupt many mechanisms regulating mitochondrial dynamics. The result is self-amplifying inflammation oxidative stress and mitochondrial dysfunction within the EC and potentially an increase in systemic inflammation

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