Protection of DDAH2 overexpression against homocysteine-induced impairments of DDAH/ADMA/NOS/NO pathway in endothelial cells.

Background/aims: Homocysteine-induced endothelial dysfunction favors the development of cardiovascular diseases through accumulation of endogenous nitric oxide (NO) synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) is the major enzyme for the degradation of ADMA in endothelial cells. The purpose of this study was to determine whether suppressed DDAH2 expression contributed to impairments of DDAH/ADMA/NOS/NO pathway induced by homocysteine in endothelial cells and whether DDAH2 overexpression could prevent endothelial cell dysfunction caused by homocysteine.

Ex vivo gene transferring of human dimethylarginine dimethylaminohydrolase-2 improved endothelial dysfunction in diabetic rat aortas and high glucose-treated endothelial cells.

Objectives: Elevated level of asymmetric dimethylarginine (ADMA) is an independent risk factor for endothelial dysfunction. Dimethylarginine dimethylaminohydrolase (DDAH) is the key enzyme responsible for the degradation of endogenous ADMA. The purposes of this study were to determine whether suppressed DDAH2 expression would implicate in endothelial dysfunction associated with diabetes mellitus and further to investigate whether adenovirus-mediated DDAH2 gene overexpression could improve the hyperglycemia-induced endothelial dysfunction.