Fig. 1.

Overview of the mechanisms affected by TLR4 following stimulation of vascular NADPH oxidase in diabetes. Hyperglycemia itself or in combination with other DAMPs modulates the expression of the TLR4-MD2 complex. TLR4 induces the activation of NADPH oxidase leading to exacerbated production of ROS in the vascular system. Excessive levels of ROS disrupt key signaling pathways, ultimately reducing the availability of NO, increasing the production of pro-inflammatory cytokines and the activation status of MAPKs, which in turn impacts the RAS system in the kidneys. Together, these alterations might account for an increase in blood pressure. Excitingly, blockade of the TLR4-MD2 complex lowers blood pressure, reduces low-grade inflammation, and attenuates ROS levels, improving vascular function in murine animals. Created with BioRender.com.