Risk factors for vascular remodeling, such as hypertension, endothelial dysfunction, diabetes, and atherosclerotic plaques, and vascular injury during stenting are associated with reductions in the antioxidant enzyme GPX1. Reductions in GPX1 lead to redox stress, with increases in both reductive stress via GSH and oxidative stress via enhanced production of superoxide (O₂^.–), hydrogen peroxide (H₂O₂), and peroxynitrite (OONO^–). Reductive stress in turn increases s-glutathionylation of key proteins, which in VSMCs, leads to their proliferation, migration, and survival, contributing to in-stent stenosis. Oxidative stress modifies DNA, lipids, and proteins and is known to affect pathways associated with key risk factors (pink box) to exacerbate vasculopathies. It is highly likely that reductive stress via s-glutathionylation of important proteins contributes to vascular remodeling associated with these risk factors. In this issue of the JCI, Ali et al. (10) identify GPX1 as the network hub gene capable of mediating both reductive and oxidative stress in VSMCs. Perturbations in reductive stress may turn out to be as important, if not more important, than oxidative stress, as demonstrated in in-stent stenosis, with clinical implications that may extend beyond BAS.