TY - DATA T1 - Therapeutic Effects of Cordycepin on Monocrotaline-induced Pulmonary Arterial Hypertension in Rats via cGMP/PKG/PPAR-γ Signaling Pathway PY - 2022/08/22 AU - Jiangpeng Lin UR - https://data.4tu.nl/articles/dataset/Therapeutic_Effects_of_Cordycepin_on_Monocrotaline-induced_Pulmonary_Arterial_Hypertension_in_Rats_via_cGMP_PKG_PPAR-_Signaling_Pathway/20517948/1 DO - 10.4121/20517948.v1 KW - Cordycepin KW - cGMP KW - PKG KW - PPAR-γ KW - Pulmonary arterial hypertension (PAH) N2 -

Cordycepin can relax the blood vessels and inhibit vascular remodeling. In this study, we investigate the effects of Cordycepin on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and its underlying mechanism. After 28 days of intragastric Cordycepin administration (50 mg/kg), the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of rats with PAH are seen to decrease significantly. HE staining is used to evaluate pulmonary vascular remodeling, and Cordycepin is found to reduce it in rats with PAH. ELISA shows that cGMP is significantly increased in plasma from the Cordycepin group. Compared with the MCT group, Cordycepin can increase the protein expression levels of PKG and PPAR-γ. In cell experiments, the optimum concentration of Cordycepin on pulmonary artery smooth muscle cells (PASMCs) is found to be 50 μM by CCK-8 assay. In scratch experiments, Cordycepin is shown to inhibit the migration of PASMCs to a large extent. EDU and TUNEL experiments show that Cordycepin can inhibit the proliferation and promote the apoptosis of PASMCs. Western blot results show that PCNA expression decreases, BAX/Bcl-2 expression increases, Caspase3 expression increases and PKG and PPAR-γ protein expression increases in Cordycepin-treated PASMCs. However, the PKG inhibitor (HA-100) and PPAR-γ inhibitor (T0070907) can reverse this process, promote the proliferation of PASMCs, inhibit apoptosis and reduce the expression of PKG and PPAR-γ. Cordycepin can increase the expression of cGMP compared with the MCT group. In conclusion, Cordycepin may improve rat PAH and other specific mechanisms by enhancing the cGMP/PKG/PPAR-γ signaling pathway. As such, it may be a candidate drug for PAH treatment.

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