Stacy Wendell

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Therapeutic Targeting of Vascular Subphenotypes of Lung Disease

PROJECT NARRATIVE In our tPPG, we have proposed that pulmonary vascular disease is a relatively under-studied, but important sub-phenotype in the broader setting of chronic heart and lung diseases, increasing disease severity and complicating therapy. Pathological pulmonary vascular remodeling occurs in subsets of patients in the setting of left heart diastolic dysfunction, the metabolic syndrome, and is a secondary event in advanced lung diseases. The development of pulmonary hypertension (PH) in these settings is further modulated by host genetics, diet, and microbiome and the development of the most effective specific therapy likely requires dual targeting of the underlying conditions, such as metabolic syndrome and the pulmonary vascular sub-phenotype. Based on extensive data generated over the last cycle of this tPPG, we hypothesize that new nitrate, nitrite, and nitro-fatty acid based therapies, that have now successfully advanced through human phase 1 safety testing, will target both the metabolic syndrome and the pulmonary vasculature, to limit disease progression in patients with this PH sub-phenotype.