Novel therapeutic targets of pulmonary hypertension.
Novel therapeutic targets of pulmonary hypertension.
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肺动脉高压的新治疗靶点。
DOI：
10.1161/atvbaha.116.308263
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Shimokawa H.
中科院分区：
文献类型：
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作者：
Yaoita N;Satoh K;Shimokawa H.
在慢性缺氧条件下，vsmc特异性rock2缺陷小鼠的动脉粥样硬化血栓血管活性显著增加，PH和RV肥大的发展受到抑制。24此外，静脉注射其他rho激酶抑制剂可改善大鼠的全身和肺动脉压。27,28事实上，我们通过肺免疫染色或评估PAH患者中性粒细胞中岩石的活性获得了rho激酶激活的直接证据。23此外，我们证明了法舒地尔和西地那非联合治疗通过抑制单罗塔林诱导的PH大鼠的ROCKs活性显示出额外的效果。这些结果表明rhoa - rho激酶信号通路是PAH新的治疗靶点。
e98 Arterioscler Thromb Vasc Biol December 2016 activity were significantly increased in response to chronic hypoxia, and the development of PH and RV hypertrophy was suppressed in VSMC-specific ROCK2-deficient mice. 24 Furthermore, systemic and pulmonary arterial pressure was improved with intravenous injection of other Rho-kinase inhibitors in rats. 27, 28 Indeed, we obtained direct evidence for Rho-kinase activation with immunostaining of lung or evaluating the activity of ROCKs in neutrophil from patients with PAH. 23 Furthermore, we demonstrated that the combination therapy using fasudil and sildenafil showed additional effects through inhibition of ROCKs activity in monocrotaline-induced PH rats. 21 These results indicate that RhoA–Rho-kinase signaling pathways are the novel therapeutic targets of PAH.