Mechanisms for Nogo-B mediating mitochondrial reactive oxygen species generation during vascular remodeling in mice / 中华老年医学杂志

ABSTRACT

Objective:To investigate the role of Nogo-B in mitochondrial reactive oxygen species(m-ROS)production and vascular remodeling in vascular smooth muscle cells(VSMCs), and to further clarify the molecular mechanism for Nogo-B in m-ROS production via regulating ATP synthase expression.Methods:A mouse model of vascular remodeling was established.The expression of Nogo-B in mouse smooth muscle cells was detected.Forty mice were divided into the AAV-NC+ control, AAV-NC+ angiotensin Ⅱ(AngⅡ), AAV-Nogo-B+ control and AAV-Nogo-B+ AngⅡ groups(n=10 for each group). VSMCs cultured in vitro were divided into the control group and the Nogo-B overexpression group(Ad-Nogo-B). The expression of Nogo-B in VSMCs in vitro stimulated with AngⅡ was detected.Through experiments conducted in vivo, Nogo-B was overexpressed in VSMCs, then VSMCs were stimulated with AngⅡ, and m-ROS production, tissue fibrosis and mitochondrial function were examined.The regulatory effects of Nogo-B on m-ROS production were explored.Molecular mechanisms for NoGO-B in vascular remodeling via regulating ATP synthase/m-ROS production were examined. Results:Compared with the control group, the expression of Nogo-B was decreased in VSMCs treated with AngⅡ(0.36±0.13 vs.1.00±0.13, t=8.44, P<0.05). The production of m-ROS, fibrosis and mitochondrial dysfunction were increased in VSMCs during vascular remodeling( P<0.05), while overexpression of Nogo-B significantly reduced m-ROS production, fibrosis and mitochondrial dysfunction( P<0.05). ATP synthase expression in VSMCs was positively regulated by Nogo-B.ATP synthase expression was higher in the AAV-Nogo-B+ AngⅡ group than in the AAV-NC+ AngⅡ group(0.86±0.14 vs.0.49±0.17, t=-3.97, P<0.05). The production of m-ROS was reduced by Nogo-B and was lower in the AAV-Nogo-B+ AngⅡ group than in the AAV-NC+ AngⅡ group(1.28±0.34 vs.3.26±0.57, t=7.18, P<0.05). Meanwhile, the ability of Nogo-B to mitigate the deleterious effects of oxidative stress in VSMCs could be offset by oligomycin. Conclusions:Nogo-B participates in vascular remodeling by regulating ATP synthase-mediated m-ROS production.