Involvement of CapG in proliferation and apoptosis of pulmonary arterial smooth muscle cells and in hypoxia-induced pulmonary hypertension rat model.
OBJECTIVE
Actin-binding protein capping protein gelsolin-like (CapG) was preferentially expressed in human pulmonary arterial smooth muscle cells (PASMCs) under hypoxia, and reduced CapG expression was accompanied by impaired migration ability in vitro. We intended to investigate the effects of CapG on rat PASMCs and hypoxia-induced pulmonary hypertension (HPH) rat model.


METHODS
We investigated the effect of RNA interference-medicated down-regulation of CapG expression in rat PASMCs as well as in HPH rat model. The proliferation, apoptosis and cell cycle of PASMCs were evaluated. The HPH rat model was established by intratracheal instillation of lentiviral vector and subsequent hypoxia exposure for four weeks. Right ventricular systolic pressure, right ventricular hypertrophy and the percentage of medial wall thickness were measured to evaluate the development of HPH.


RESULTS
Knock-down CapG in PASMCs resulted in decreased proliferation, increased apoptosis and induced cell cycle inhibition. Down-regulation of CapG expression locally could attenuate pulmonary hypertension, pulmonary vascular remodeling and right ventricular hypertrophy in HPH rat model.


CONCLUSIONS
Our study indicated that CapG participated in the pathogenesis of pulmonary vascular remodeling in HPH rats, which was probably mediated by promoting the proliferation and inhibiting the apoptosis of PASMCs. We proposed CapG modulating protective effects of pulmonary hypertension.
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Xiaoling
X
Xu
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Huihui
H
Hu
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Xiaohua
X
Wang
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Wu
W
Ye
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Hua
H
Su
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Yanjie
Y
Hu
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Liangliang
L
Dong
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Ruifeng
R
Zhang
a Department of Respiratory Medicine , Sir Run Run Shaw Hospital , Zhejiang University School of Medicine , Hangzhou, Zhejiang , China.
Kejing
K
Ying
D051344:Actin Capping Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D018260:Gelsolin / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D011651:Pulmonary Artery / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D066253:Vascular Remodeling / Q000502:physiology
D051344:Actin Capping Proteins; D018260:Gelsolin
capping protein gelsolin-like; hypoxia-induced pulmonary hypertension; lentiviral vector; pulmonary arterial smooth muscle cells; vascular remodeling