Fig. 12. Proposed signalling pathway of asymmetric methylarginine (ADMA). ADMA inhibits NO production in PAECs. This contributes to a decrease in RhoA phosphorylation on Ser188 which facilitates it membrane localisation and activation. Phosphorylation of RhoA on Ser188 is likely to be carried out by protein kinase G (PKG) but other kinases, such as protein kinase A (PKA) may also be involved. Activation of RhoA and its downstream effector, Rho kinase inhibits endothelial motility, possibly by increasing cell adhesion to the substratum or slowing down turnover of focal adhesions. Impairment of endothelial motility inhibits angiogenic responses of endothelial cells. Enzymes metabolising ADMA, dimethylarginine dimethylaminohydrolases (DDAH) improve persistence of cell movement and prevent the effects of ADMA on cells.