Protandim Study #12 as we’re calling it, focuses on Protandim’s ability to reduce hypertension and what it can mean for human intervention in future studies. This is followup review from the previous VCU study published in the American Heart Association study, and adds:
Significance: Pathobiological mechanisms which contribute to pulmonary vasoconstriction, lung vascular remodeling and the development of right heart failure include the generation of reactive oxygen and nitrogen species and the response of lung vascular and cardiac cells to these molecules. We review the information regarding oxidant stress balanced by antioxidant mechanisms and the role of oxidants and antioxidants in hypoxic pulmonary hypertension and their potential role in an animal model of severe pulmonary arterial hypertension (PAH). Recent Advances: In human lung tissue from patients with idiopathic PAH we find reduced SOD activity and high expression of the oxidant stress markers nitrotyrosine and 8-OH-guanosine. In the Sugen 5416/chronic hypoxia model of PAH lung tissue expression of nitrotyrosine and hemeoxygenase 1 (HO-1) is substantial, while HO-1 expression in the failing right ventricle is decreased. This model, based on administration of the VEGF receptor blocker Sugen 5416 and chronic hypoxia (Su/Hx), reproduces many of the characteristic features of severe angioobliterative human PAH. Treatment of Su/Hx rats with ‘protandim,’ which Nrf-2-dependently upregulates the expression of genes encoding antioxidant enzymes, protects against right heart failure without affecting angioobliterative PAH. Critical Issues: In human severe PAH, patient survival is determined by the function of the stressed right ventricle; investigation of oxidative and nitrosative stresses and their potential contribution to right heart failure is necessary. Future Directions: Antioxidant therapeutic strategies may be of benefit in the setting of human severe PAH. Whether antioxidant strategies affect lung vascular remodeling and/or prevent right heart failure remains to be examined.