医学
内科学
缺氧(环境)
心室重构
MAPK/ERK通路
肺动脉高压
心脏病学
药理学
拜瑞妥
右心室肥大
血压
内分泌学
肺动脉
西地那非
内皮素1
作者
Hideki Imano,Ryuji Kato,Atsuo Nomura,Maki Tamura,Yudai Yamaguchi,Yoshio Ijiri,Hong Wu,Takashi Nakano,Yoshikatsu Okada,Takehiro Yamaguchi,Yasukatsu Izumi,Minoru Yoshiyama,Michio Asahi,Tetsuya Hayashi
标识
DOI:10.1248/bpb.b20-01011
摘要
Pulmonary arterial hypertension (PAH) is a progressive condition that frequently results in right ventricular (RV) remodeling. The objectives of this study are to investigate effects of rivaroxaban on RV remodeling in a rat model of PAH, created with Sugen5416 and chronic hypoxia, and the in vitro effects of rivaroxaban on human cardiac microvascular endothelial cells (HCMECs). To create the PAH model, male Sprague-Dawley rats were subcutaneously injected with Sugen5416 (20 mg/kg) and exposed to 2 weeks of hypoxia (10% O2), followed by 2 weeks of exposure to normoxia. The animals were then divided into 2 groups with or without administration of rivaroxaban (12 mg/kg/d) for a further 4 weeks. HCMECs were cultured under hypoxic conditions (37 °C, 1% O2, 5% CO2) with Sugen5416 and with or without rivaroxaban. In the model rats, RV systolic pressure and Fulton index increased by hypoxia with Sugen5416 were significantly decreased when treated with rivaroxaban. In HCMECs, hypoxia with Sugen5416 increased the expression of protease-activated receptor-2 (PAR-2) and the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB), while treatment with rivaroxaban significantly suppressed the expression of these proteins. Rivaroxaban attenuated RV remodeling in a rat model of PAH by reducing ERK, JNK and NF-κB activation. Rivaroxaban has the possibility of providing additive effects on RV remodeling in patients with PAH.
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