Compartmentalization of Redox-Regulated Signaling in the Pulmonary Circulation

Oxidative stress is well recognized to contribute to the pathogenesis of diverse diseases, including the devastating disease of the lung's blood vessels, pulmonary arterial hypertension (PAH), however, antioxidant-based therapies have been overall disappointing. With the evolution of the field of redox biology, it is now becoming clear that redox reactions are highly selective and targeted, allowing for precise control of redox-regulated signaling in health and disease. This special Forum of the journal describes the current state of knowledge on the regulation of redox-regulated signaling during the development of pulmonary vascular disease, focusing on distinct compartmentalized mechanisms outside and within the cell, including regulation of extracellular and intracellular membrane receptors and channels; responses to changes in biomechanical forces; intracellular thiol redox control; regulation of the nuclear transcription factor, peroxisome proliferator-activated receptor-γ; and regulation of mitochondrial metabolism. Collectively, they exemplify the complex, precise, and localized signaling pathways that drive PAH pathogenesis. This group of authors suggests ways that our increased understanding of these events may pave the way to improved therapeutic approaches for the treatment of this lethal disease.