Redox balance dynamically regulates vascular growth and remodeling

Vascular growth and remodeling responses entail several complex biochemical, molecular, and cellular responses centered primarily on endothelial cell activation and function. Recent studies reveal that changes in endothelial cell redox status critically influence numerous cellular events that are important for vascular growth under different conditions. It has been known for some time that oxidative stress actively participates in many aspects of angiogenesis and vascular remodeling. Initial studies in this field were largely exploratory with minimal insight into specific molecular mechanisms and how these responses could be regulated. However, it is now clear that intracellular redox mechanisms involving hypoxia, NADPH oxidases (NOX), xanthine oxidase (XO), nitric oxide and its synthases, and intracellular antioxidant defense pathways collectively orchestrate a redox balance system whereby reactive oxygen and nitrogen species integrate cues controlling vascular growth and remodeling. In this review, we discuss key redox regulation pathways that are centrally important for vascular growth in tissue health and disease. Important unresolved questions and issues are also addressed that requires future investigation.