Reoxygenation Reverses Hypoxic Pulmonary Arterial Remodeling by Inducing Smooth Muscle Cell Apoptosis via Reactive Oxygen Species–Mediated Mitochondrial Dysfunction

BackgroundPulmonary arterial remodeling, a main characteristic of hypoxic pulmonary hypertension, can gradually reverse once oxygen has been restored. Previous studies documented that apoptosis increased markedly during the reversal of remodeled pulmonary arteries, but the types of cells and mechanisms related to the apoptosis have remained elusive. This study aimed to determine whether pulmonary artery smooth muscle cell (PASMC)‐specific apoptosis was involved in the reoxygenation‐induced reversal of hypoxic pulmonary arterial remodeling and elucidate the underlying mechanism. Methods and ResultsHypoxic pulmonary hypertension was induced in adult male Sprague‐Dawley rats (n=6/group) by chronic hypobaric hypoxia. and the hypoxic pulmonary hypertension rats were then transferred to a normoxia condition. During reoxygenation, hypoxia‐induced pulmonary arterial remodeling gradually reversed. The reversal of remodeled pulmonary arteries was associated with increased H2O2 and with changes in lung expression of...