Olmesartan, an AT1 antagonist, attenuates oxidative stress, endoplasmic reticulum stress and cardiac inflammatory mediators in rats with heart failure induced by experimental autoimmune myocarditis.
Olmesartan, an AT1 antagonist, attenuates oxidative stress, endoplasmic reticulum stress and cardiac inflammatory mediators in rats with heart failure induced by experimental autoimmune myocarditis.
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DOI：
10.7150/ijbs.7.154
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发表时间：
2011-02-11
影响因子：
9.2
通讯作者：
Kodama M
中科院分区：
文献类型：
--
作者：
Sukumaran V;Watanabe K;Veeraveedu PT;Gurusamy N;Ma M;Thandavarayan RA;Lakshmanan AP;Yamaguchi K;Suzuki K;Kodama M
研究表明，血管紧张素II参与了免疫和炎症反应，可能有助于免疫介导的疾病的发病机制。最近的证据表明，氧化应激可能在心肌炎中发挥作用。在这里，我们研究了AT 1 R拮抗剂奥美沙坦是否通过抑制氧化应激、内质网（ER）应激和炎症细胞因子来预防实验性自身免疫性心肌炎（EAM）。通过用猪心肌肌球蛋白免疫刘易斯大鼠诱导EAM，将其分为两组，并用奥美沙坦（10 mg/kg/天）或溶剂处理21天。与溶媒组大鼠相比，奥美沙坦治疗组通过血流动力学和超声心动图分析测量的心肌功能参数显著改善。与溶剂组大鼠相比，奥美沙坦组大鼠心肌促炎细胞因子[白细胞介素（IL）-1β、单核细胞趋化蛋白-1、肿瘤坏死因子-α和干扰素-γ]的mRNA表达和肿瘤坏死因子-α的蛋白表达减弱。奥美沙坦治疗组大鼠心肌AT 1 R、NADPH氧化酶亚单位（p47 phox、p67 phox、gp 91 phox）蛋白表达、氧化应激标志物（3-硝基酪氨酸和4-羟基-2-壬烯醛）表达及心肌细胞凋亡均显著低于对照组。此外，奥美沙坦治疗下调心肌葡萄糖调节蛋白-78，生长停滞和DNA损伤诱导基因，caspase-12，磷酸化p38丝裂原活化蛋白激酶（MAPK）和磷酸化JNK的表达。这些发现表明，奥美沙坦至少部分通过抑制氧化应激、ER应激和炎性细胞因子来保护大鼠免受EAM。
Studies have demonstrated that angiotensin II has been involved in immune and inflammatory responses which might contribute to the pathogenesis of immune-mediated diseases. Recent evidence suggests that oxidative stress may play a role in myocarditis. Here, we investigated whether olmesartan, an AT1R antagonist protects against experimental autoimmune myocarditis (EAM) by suppression of oxidative stress, endoplasmic reticulum (ER) stress and inflammatory cytokines. EAM was induced in Lewis rats by immunization with porcine cardiac myosin, were divided into two groups and treated with either olmesartan (10 mg/kg/day) or vehicle for a period of 21 days. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Treatment with olmesartan attenuated the myocardial mRNA expressions of proinflammatory cytokines, [Interleukin (IL)-1β, monocyte chemoattractant protein-1, tumor necrosis factor-α and interferon-γ)] and the protein expression of tumor necrosis factor-α compared with that of vehicle-treated rats. Myocardial protein expressions of AT1R, NADPH oxidase subunits (p47phox, p67phox, gp91phox) and the expression of markers of oxidative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), and the cardiac apoptosis were also significantly decreased by the treatment with olmesartan compared with those of vehicle-treated rats. Furthermore, olmesartan treatment down-regulated the myocardial expressions of glucose regulated protein-78, growth arrest and DNA damage-inducible gene, caspase-12, phospho-p38 mitogen-activated protein kinase (MAPK) and phospho-JNK. These findings suggest that olmesartan protects against EAM in rats, at least in part via suppression of oxidative stress, ER stress and inflammatory cytokines.
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影响因子：
4.6
作者：
Fuse, K;Kodama, M;Aizawa, Y
通讯作者：
Aizawa, Y
影响因子：
4.8
作者：
Habibi, Javad;Whaley-Connell, Adam;Sowers, James R.
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Sowers, James R.
影响因子：
37.8
作者：
KODAMA, M;MATSUMOTO, Y;FUJIWARA, M
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FUJIWARA, M
影响因子：
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作者：
Jia, N;Okamoto, H;Kitabatake, A
通讯作者：
Kitabatake, A
影响因子：
5.3
作者：
Hamada, H;Suzuki, M;Aoe, T
通讯作者：
Aoe, T