Hepcidin protects pulmonary artery hypertension in rats by activating NF-κB/TNF-α pathway

W.-Y. Liu, L. Wang, Y.-F. Lai

Department of Cardial Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. laiyongfeng86@outlook.com

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• Cardiology

OBJECTIVE: The pulmonary artery hypertension (PAH) model was established in rats in this study. Therefore, we aimed to elucidate the protective role of Hepcidin in PAH rats and its underlying mechanism.

MATERIALS AND METHODS: 24 male Sprague Dawley (SD) rats were randomly divided into sham group, PAH group and Hepcidin group, with 8 rats in each group. After animal procedures, hemodynamic parameters and right ventricular hypertrophy indexes were determined in rats. Cytokines in serum samples of rats were detected by enzyme-linked immunosorbent assay (ELISA). Pathological lesions in lung tissues were observed by hematoxylin and eosin (H&E) staining. Finally, Western blot was conducted to detect the protein expressions of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) in lung tissues of rats.

RESULTS: Compared with sham group, mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) were significantly elevated in rats of PAH group (p<0.05). On the contrary, mPAP and RVSP in rats of Hepcidin group were both significantly lower than PAH group (p<0.05). Hepcidin treatment attenuated PAH-induced pathological lesions in lung tissues. ELISA results elucidated that Hepcidin treatment significantly decreased serum levels of TGF-β, TNF-α, IL-1β, and IL-6. In addition, Western blot results demonstrated that protein levels of NF-κB, TNF-α, IL-1β, VCAM-1, ICAM-1, and MCP-1 in Hepcidin group were remarkably lower than those of PAH group.

CONCLUSIONS: Hepcidin alleviates inflammatory response in PAH rats by inhibiting NF-kB/ TNF-α pathway.

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