Figure 2.

The signaling mechanisms involved in upregulation of vascular arginase expression/activity in vascular endothelial cells (EC). Various cardiovascular risk factors such as hyperinsulinemia, aging, hyperglycemia, hypoxia, etc., upregulate Arg-I or/and Arg-II expression/activity through signaling pathways including p38MAPK, mTORC1-S6K, Rho/ROCK, and JAK/STAT6, leading to eNOS-uncoupling that ultimately causes vascular oxidative stress and inflammation contributing to the development of vascular diseases. Moreover, the mutual positive regulation between S6K1 and Arg-II gene expression accelerates oxidative stress and inflammation through eNOS-uncoupling.