Reducing damage through Nrf-2.

摘要

The first paper by Velmurugan et al. started from the observation that reactive oxygen species (ROS) play an important "role in the generation of myogenic tone in the microvasculature, i.e. in response to an acute increase in intraluminal pressure, vessels produce a burst of ROS that increases vessel contraction, as demonstrated in their study. This phenomenon is amplified in diabetes (type I and II), which is also associated with excessive production of various oxidant radicals; the latter may result from the dysregulation of the anti-oxidant defence mechanisms normally orchestrated by Nrf-2, which is reduced in diabetes.1 Therefore, the authors examined the hypothesis that excessive ROS contribute to microvascular dysfunction in a mouse type II diabetes model (db/ db mice), and whether this could be reversed by up-regulating Nrf-2. Indeed, by combining pressure myograph and in situ ROS measurements in mounted vessels, they show that the burst of ROS evoked by increased intraluminal pressure is strikingly greater in diabetic arterioles, together with increased myogenic tone. Moreover, the phenotype is associated with a decreased content of reduced GSH in the vessels to-getherwith decreased Nrf-2 transcripts and proteins.