Increased Cyr61 in pulmonary arterial hypertension involving in proliferation of pulmonary arterial smooth muscle cells
Zhuoli Zhang (Beijing, China), Yong Fan (Beijing, China), Zhuoli Zhang, Lan Gao, Yong Fan, Yanjie Hao, Wei Zhou
Source: International Congress 2016 – Pulmonary hypertension and pulmonary embolism: from the bench to the bedside
Disease area: Pulmonary vascular diseases
Abstract Objectives: To evaluate the expression of Cyr61 in PAH patients and investigate the effect of Cyr61 on proliferation of PASMCs in PAH rats and the mechanism. Methods: Collecting the plasma of CTD-PAH,CTD without PAH,IPAH and healthy control patients, ELISA was used to detect the level of Cyr61.Next,specific pathogen free grade male Sprague Dawley rats were divided into monocrotaline induced PAH model group and normal control group. Lung tissues and pulmonary arteries of rats were collected and the PASMCs were dissected and cultivated.Expression of Cyr61 in the lung tissues, pulmonary arteries and PASMCs were tested by immunohistochemical staining (IHC), Western blot and Real-time PCR. Meanwhile,PASMCs from both group rats were stimulated by exogenous recombinant Cyr61 protein, Cell Counting Kit-8 (CCK8) was used to identify cell proliferation. At last, RNA interference (RNAi) was used to inhibit the endogenous expression of Cyr61 in PASMCs,and the expression of p-AKT and AKT and the proliferation of PASMCs were analysed.Results: Plasma level of Cyr61 in the PAH patients were significant higher than that of CTD without PAH and healthy control. Compared with control rats, Cyr61 was overexpressed in the lung tissue and PASMCs of PAH rats. Exogenous recombinant Cyr61 protein could promote the proliferation of PASMCs from two groups of rats. While the expression of Cyr61 in PASMCs was inhibited by RNAi,cell proliferation was restrained and the expression of p-AKT declined.Conclusions: Level of Cyr61 in the plasma of PAH patients was highly increased.Cyr61 could promote PASMCs proliferation via AKT pathway,which indicated Cyr61 may play a role in the pathogenesis of PAH.
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Zhuoli Zhang (Beijing, China), Yong Fan (Beijing, China), Zhuoli Zhang, Lan Gao, Yong Fan, Yanjie Hao, Wei Zhou. Increased Cyr61 in pulmonary arterial hypertension involving in proliferation of pulmonary arterial smooth muscle cells. Eur Respir J 2016; 48: Suppl. 60, 2477
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