Involvement of CapG in proliferation and apoptosis of pulmonary arterial smooth muscle cells and in hypoxia-induced pulmonary hypertension rat model

ABSTRACT

Purpose: 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. Materials and 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.

KEYWORDS:

• capping protein gelsolin-like
• pulmonary arterial smooth muscle cells
• hypoxia-induced pulmonary hypertension
• vascular remodeling
• lentiviral vector

Additional information

Funding

This study was supported by research grants 81570043 and 81270107 from the National Natural Science Foundation of China, and research grant LY14H010001 from the Natural Science Foundation of Zhejiang Province in China.