Involvement of Reductive Stress in the Cardiomyopathy in Transgenic Mice With Cardiac-Specific Overexpression of Heat Shock Protein 27
Involvement of Reductive Stress in the Cardiomyopathy in Transgenic Mice With Cardiac-Specific Overexpression of Heat Shock Protein 27
复制标题
还原应激与心脏特异性过表达热休克蛋白 27 的转基因小鼠心肌病的关系
DOI：
10.1161/hypertensionaha.109.147066
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发表时间：
2010-06-01
期刊：
影响因子：
8.3
通讯作者：
Liu, Li
中科院分区：
文献类型：
--
作者：
Zhang, Xia;Min, Xiaoyan;Liu, Li
氧化应激在心脏疾病中起着重要的作用，这已经得到了很好的证明，而还原性应激的作用却很少被研究。我们和其他人之前已经证明热休克蛋白27 （Hsp27）起着抗氧化剂的作用。为了研究Hsp27过表达是否会导致应激减轻并导致心肌病，我们制备了不同Hsp27表达水平的转基因小鼠。我们观察到高水平Hsp27的转基因小鼠发生心肌病。肌病心脏处于还原性应激状态，还原性谷胱甘肽/氧化性谷胱甘肽比值升高，活性氧水平降低。此外，肌病心脏谷胱甘肽过氧化物酶1上调，铁含量降低。更重要的是，抑制谷胱甘肽过氧化物酶1显著减轻心肌病的发展。这些数据表明，hsp27诱导的心肌病可能至少部分归因于谷胱甘肽过氧化物酶1的上调。我们的研究结果表明，减压在心肌病的发展中起着重要作用，Hsp27可能作为治疗心肌病患者的潜在靶点。[中国高血压杂志];2010;55:1412-1417.]
Oxidative stress plays an important role in cardiac diseases, which has been well demonstrated, whereas the role of reductive stress has been poorly investigated. We and others have shown previously that heat shock protein 27 (Hsp27) plays a role as an antioxidant. To investigate whether overexpression of Hsp27 could lead to reductive stress and result in cardiomyopathy, we generated transgenic mice with different expression levels of Hsp27. We observed that transgenic mice with high levels of Hsp27 developed cardiomyopathy. The myopathic hearts were under reductive stress, which was evidenced by an increased ratio of reduced glutathione/oxidized glutathione and a decreased level of reactive oxygen species. In addition, upregulated glutathione peroxidase 1 and decreased iron content were revealed in the myopathic hearts. More importantly, inhibition of glutathione peroxidase 1 significantly attenuated the development of cardiomyopathy. The data indicate that the Hsp27-induced cardiomyopathy could be attributed to, at least in part, upregulation of glutathione peroxidase 1. Our findings suggest that reductive stress plays an important role in the development of cardiomyopathy and that Hsp27 may serve as a potential target for the treatment of patients with cardiomyopathy. (Hypertension. 2010; 55: 1412-1417.)