Study on roles of a novel NADPH oxidase isoform in the development of idiopathic pulmonary arterial hypertention

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Pulmonary arterial hypertension is characterized by hypertrophy of small pulmonary arteries, which leads to right ventricular (RV) hypertrophy and heart failure. Nox1 is a catalytic subunit of NADPH oxidase known as a major source of superoxide production in vascular tissues. In Nox1-defcient mice (Nox1-/Y) hypertrophy of small pulmonary arteries and RV wall were observed. A significant decrease in number of apoptotic cells were demonstrated in pulmonary arterial smooth muscle cells (PASMC) isolated from Nox1-/Y. Dysfunction of Kv1.5, a voltage-dependent potassium channel, is one of the features reported in human and experimental PAH. A significant decrease in Kv1.5 protein and an increase in intracellular potassium levels were observed in Nox1-/Y PASMC.These results suggest that Nox1 plays a critical role in apoptosis of PASMC by regulating Kv1.5 expression and intracellular potassium levels.