Open AccessReoxygenation Reverses Hypoxic Pulmonary Arterial Remodeling by Inducing Smooth Muscle Cell Apoptosis via Reactive Oxygen Species–Mediated Mitochondrial Dysfunction
Author(s) -
Chen Jian,
Wang YanXia,
Dong MingQing,
Zhang Bo,
Luo Ying,
Niu Wen,
Li ZhiChao
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.005602
Subject(s) - apoptosis , hypoxia (environmental) , medicine , pulmonary hypertension , reactive oxygen species , cytochrome c , mitochondrion , pulmonary artery , mitochondrial ros , endocrinology , pharmacology , oxidative stress , biology , oxygen , microbiology and biotechnology , chemistry , biochemistry , organic chemistry
Background Pulmonary 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 Results Hypoxic 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 H 2 O 2 and with changes in lung expression of cleaved caspase3/ PARP , Bax, and Bcl‐2, consistent with increased apoptosis. The PASMC apoptosis, in particular, increased remarkably during this reversal. In vitro, reoxygenation induced the apoptosis of cultured rat primary PASMC s accompanied by increased mitochondrial reactive oxygen species, mitochondrial dysfunction, and the release of cytochrome C from mitochondria to cytoplasm. Clearance of reactive oxygen species alleviated mitochondrial dysfunction as well as the release of cytochrome C and, finally, decreased PASMC apoptosis. Conclusions Reoxygenation‐induced apoptosis of PASMC s is implicated in the reversal of hypoxic pulmonary arterial remodeling, which may be attributed to the mitochondrial reactive oxygen species–mediated mitochondrial dysfunction.