Olmesartan inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch through the inhibition of the c-Jun N-terminal kinase and p38 signaling pathways
Olmesartan inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch through the inhibition of the c-Jun N-terminal kinase and p38 signaling pathways
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DOI：
10.1016/j.jphs.2014.11.002
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发表时间：
2015-01-01
影响因子：
3.5
通讯作者：
Yoshizumi, Masanori
中科院分区：
文献类型：
--
作者：
Ito, Satoyasu;Ozawa, Kentaro;Yoshizumi, Masanori
急性主动脉夹层（acute aortic dissection，AAD）是一种严重威胁生命的疾病，目前尚无有效的药物治疗方法。因此，我们假设血压的急性升高通过JNK或p38的磷酸化导致SMC死亡，这可能导致AAD。我们研究了周期性机械拉伸，这模拟了急性血压升高，对培养的大鼠主动脉平滑肌细胞（RASMCs）的影响，并检查了在INK和p38磷酸化的变化。此外，我们还研究了血管紧张素II受体阻滞剂奥美沙坦对牵张诱导RASMC死亡的影响。我们发现，机械牵张诱导RASMC死亡的时间依赖性的方式，这与JNK和p38的磷酸化。奥美沙坦抑制RASMC死亡和JNK和p38的磷酸化。JNK和p38抑制剂逆转牵张诱导的RASMC死亡。这些结果表明，急性机械牵张引起JNK和p38磷酸化，这可能导致SMC死亡，导致主动脉夹层。奥美沙坦可通过抑制JNK和p38磷酸化，用于预防主动脉夹层的药物治疗，不依赖于其降压作用。(C)2014日本药理学会。制作和主办：Elsevier B.V.
Acute aortic dissection (AAD) is a life-threating disease; however, there is almost no effective pharmacotherapy for it. An increase in c-Jun N-terminal kinase (JNK) phosphorylation and smooth muscle cell (SMC) apoptosis is observed tissues in patients with AAD. Therefore, we hypothesized that an acute rise in blood pressure leads to SMC death through phosphorylation of JNK or p38, which may cause AAD. We investigated the influence of cyclic mechanical stretch, which mimics an acute increase in blood pressure, on cultured rat aortic SMCs (RASMCs) and examined the changes in INK and p38 phosphorylation. Further, we investigated the effect of olmesartan, an angiotensin II receptor blocker, on stretch-induced RASMC death. We found that mechanical stretch-induced RASMC death in a time-dependent manner, which correlated with the phosphorylation of JNK and p38. Olmesartan inhibited RASMC death and the phosphorylation of JNK and p38. JNK and p38 inhibitors reversed stretch-induced RASMC death. These results suggest that acute mechanical stretch causes JNK and p38 phosphorylation, which may result in SMC death leading to aortic dissection. Olmesartan may be used for pharmacotherapy to prevent aortic dissection, independent of its blood pressure-lowering effect, through its inhibition of JNK and p38 phosphorylation. (C) 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V.