We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Vascular peroxidase 1 mediates hypoxia-induced pulmonary artery smooth muscle cell proliferation, apoptosis resistance and migration.
- Authors
Baiyang You; Yanbo Liu; Jia Chen; Xiao Huang; Huihui Peng; Zhaoya Liu; Yixin Tang; Kai Zhang; Qian Xu; Xiaohui Li; Guangjie Cheng; Ruizheng Shi; Guogang Zhang
- Abstract
Aims Reactive oxygen species (ROS) play essential roles in the pulmonary vascular remodelling associated with hypoxiainduced pulmonary hypertension (PH). Vascular peroxidase 1 (VPO1) is a newly identified haeme-containing peroxidase that accelerates oxidative stress development in the vasculature. This study aimed to determine the potential role of VPO1 in hypoxia-induced PH-related vascular remodelling. Methods and results The vascular morphology and VPO1 expression were assessed in the pulmonary arteries of Sprague-Dawley (SD) rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and VPO1 expression and HOCl production were significantly increased in hypoxic rats, which also exhibited obvious vascular remodelling. Furthermore, a hypoxia-induced PH model was generated by exposing primary rat pulmonary artery smooth muscle cells (PASMCs) to hypoxic conditions (3% O2, 48 h), which significantly increased the expression of NOX4 and VPO1 and the production of HOCl. These hypoxic changes were accompanied by enhanced proliferation, apoptosis resistance, and migration. In PASMCs, hypoxia-induced changes, including effects on the expression of cell cycle regulators (cyclin B1 and cyclin D1), apoptosis-related proteins (bax, bcl-2, and cleaved caspase-3), migration promoters (matrix metalloproteinases 2 and 9), and NF-κB expression, as well as the production of HOCl, were all inhibited by silencing VPO1 with small interfering RNAs. Moreover, treatment with HOCl under hypoxic conditions upregulated NF-jB expression and enhanced proliferation, apoptosis resistance, and migration in PASMCs, whereas BAY 11-7082 (an inhibitor of NF-κB) significantly inhibited these effects.
- Subjects
PATHOPHYSIOLOGY of anoxemia; REACTIVE oxygen species; PULMONARY hypertension; PEROXIDASE; SMOOTH muscle enzymes; CELL proliferation; APOPTOSIS; HYPERTENSION risk factors
- Publication
Cardiovascular Research, 2018, Vol 114, Issue 1, p188
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvx234