DDAH says NO to ADMA.

Endothelium-derived nitric oxide (NO) is vasoprotective, as it enhances endothelial cell survival and proliferation, inhibits the excessive proliferation of vascular smooth muscle cells, and suppresses the adhesion of platelets and inflammatory cells to the vessel wall.1 Substantial evidence from preclinical studies and human research indicates that impairment of the endothelial NO synthase (NOS) pathway accelerates vascular disease and increases the risk for major adverse cardiovascular events.2–5 Impairment of the NOS pathway is multifactorial, but it is increasingly apparent that circulating inhibitors of NOS play an important role. Asymmetrical dimethylarginine (ADMA) and monomethyl-L-arginine (MMA)6 are endogenous competitive inhibitors of NOS. Most human studies have focused on ADMA, as it is the more prevalent species in human plasma. Plasma ADMA is elevated in patients with cardiovascular disease or with risk factors, and it contributes to vascular resistance and stiffness.7,8 Notably, several large studies have shown that plasma ADMA is an independent biomarker for cardiovascular morbidity and total mortality.4,5,9 Accordingly, endogenous mechanisms that regulate ADMA are deserving of further scientific attention.