Tissue-specific augmentation of circadian PAI-1 expression in mice with streptozotocin-induced diabetes
Tissue-specific augmentation of circadian PAI-1 expression in mice with streptozotocin-induced diabetes
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DOI：
10.1016/j.thromres.2004.05.011
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发表时间：
2004-01-01
影响因子：
7.5
通讯作者：
Ishida, N
中科院分区：
文献类型：
--
作者：
Oishi, K;Ohkura, N;Ishida, N
糖尿病与心脏事件的过度风险相关，梗死的风险部分由纤溶酶原激活物抑制剂-1 （PAI-1）决定。我们发现链脲佐菌素（STZ）诱导的糖尿病小鼠血浆总PAI-1水平和活性PAI-1水平以昼夜节律方式升高。PAI-1 mRNA在肺、心脏、肝脏和肾脏的昼夜表达以组织特异性方式增加。峰对峰比较显示，mRNA表达水平在心脏、肺、肝脏和肾脏分别增加了1.7倍、1.7倍、1.2倍和1.6倍。相比之下，时钟基因mPer2在糖尿病小鼠中的昼夜节律表达被保留，这表明PAI-1 mRNA的表达改变并不是因为生物钟受损而引起的。我们的研究结果表明，糖尿病引起的凝血和纤溶系统损伤部分是由于mRNA表达水平上昼夜节律PAI-1波动受损。(C) 2004 Elsevier Ltd.版权所有。
Diabetes is associated with an excess risk of cardiac events, and the risk for infarction is partly determined by plasminogen activator inhibitor-1 (PAI-1). We found that plasma total and active PAI-1 levels increased in a circadian manner in mice with streptozotocin (STZ)-induced diabetes. Circadian expression of PAI-1 mRNA in the lung, heart, liver, and kidney increased in a tissue-specific manner. Peak to peak comparisons revealed that the mRNA expression levels increased by 1.7, 1.7, 1.2, and 1.6-fold in the heart, lung, liver, and kidney, respectively. In contrast, the circadian expression of the clock gene, mPer2, was preserved in the diabetic mice, suggesting that the altered expression of PAI-1 mRNA did not arise due to impaired circadian clocks. Our results suggest that impairment of the coagulation and fibrinolytic systems induced by diabetes is partly due to impaired circadian PAI-1 fluctuation at the level of mRNA expression. (C) 2004 Elsevier Ltd. All rights reserved.