Overexpression of ACE2 prevents hypoxia-induced pulmonary hypertension in rats by inhibiting proliferation and immigration of PASMCs

H.-H. Hu, R.-F. Zhang, L.-L. Dong, E.-G. Chen, K.-J. Ying

Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Affiliated with Zhejiang University School of Medicine, Hangzhou, China. 3197061@zju.edu.cn

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• Cardiology

OBJECTIVE: Imbalance of the ratio of angiotensin converting enzyme (ACE) and ACE2 may lead to pathological conditions in lung. However, its effect on hypoxia-induced pulmonary hypertension (HPH) remains unclear. Therefore, the aim of this study was to investigate the effects of ACE2 overexpression on rat primary pulmonary arterial smooth muscle cells (PASMCs) and HPH rat model.

MATERIALS AND METHODS: ACE and ACE2 expression in rat PASMCs under hypoxia condition, as well as in HPH rat model, was detected. The overexpressed ACE2 gene was transfected into PASMCs by Lentiviral. Later, the proliferation and migration of PASMCs were evaluated. Meanwhile, the overexpressed ACE2 gene was transfected into rats and exposed to hypoxia for four weeks. Finally, the right ventricular systolic pressure, the right ventricular hypertrophy, and the percentage of the medial wall thickness were measured to evaluate the development of HPH.

RESULTS: Imbalance of the expression of ACE/ACE2 was indicated in rat PASMCs under hypoxia condition and in the HPH rat model, respectively. The overexpression of ACE2 significantly inhibited PASMCs proliferation and migration. Moreover, the overexpressed ACE2 could significantly attenuate pulmonary hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy in HPH rat model.

CONCLUSIONS: ACE2 is related to the formation of pulmonary vascular remodeling and pulmonary hypertension. Furthermore, it may prevent hypoxia-induced pulmonary hypertension by inhibiting the proliferation of PASMCs.

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