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

肺动脉高压的特征在于小肺动脉肥大，其导致右心室（RV）肥大和心力衰竭。Nox 1是NADPH氧化酶的催化亚基，被认为是血管组织中超氧化物产生的主要来源。在Nox 1-缺陷小鼠（Nox 1-/Y）中，观察到小肺动脉和RV壁肥大。从Nox 1-/Y中分离的肺动脉平滑肌细胞（PASMC）的凋亡细胞数量显著减少。Kv1.5是一种电压依赖性钾通道，其功能障碍是人类和实验性PAH的特征之一。Nox 1-/Y细胞Kv1.5蛋白表达减少，细胞内钾离子浓度升高，提示Nox 1通过调节Kv1.5蛋白表达和细胞内钾离子浓度在PASMC凋亡中起重要作用。

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.