Distinct role of nox1, nox2, and p47phox in unstimulated versus angiotensin II-induced NADPH oxidase activity in human venous smooth muscle cells.

Human saphenous veins (SV) are used for coronary bypass surgery despite the higher rate of graft failure observed as compared to arteries. A higher production of reactive oxygen species (ROS) in SV than in internal mammary artery (IMA) has been incriminated as possibly implicated in graft failure. NADPH oxidase, involved in vascular ROS production, was therefore characterized in human smooth muscle cells from SV ROS production was confirmed to be essentially NADPH oxidase dependent in cultured smooth muscle cells (SMC) from human SV and increased in comparison with IMA. To investigate the role of NADPH oxidase subunits, siRNA for noxl, nox2, or p47 phox mRNA were studied. In cultured venous SMC under unstimulated conditions, inhibition of noxl or nox2 mRNA decreased ROS production, whereas p47 phox silencing increased it. During angiotensin II (AngII) activation, nox2 or p47 phox mRNA silencing decreased ROS production, while noxl inhibition had no effect. Venous SMC express functional noxl and nox2. Only nox2 is implicated in response to AngII whilst noxl is involved in unstimulated ROS production. p47 phox negatively regulates ROS generation under basal conditions, whereas it enhances AngII increased ROS production. Thus, noxl, nox2, and p47 phox have distinct roles in NADPH oxidase activity in human veins.