Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin
Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin
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DOI：
10.1159/000090132
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发表时间：
2006-01-01
影响因子：
1.7
通讯作者：
Yokoyama, M
中科院分区：
文献类型：
--
作者：
Honjo, T;Inoue, N;Yokoyama, M
背景：尿皮质素是一种在中脑中发现的神经肽，是促肾上腺皮质激素释放因子家族的成员，在心脏组织中表达。尿皮质素在包括缺血/再灌注在内的各种病理条件下都具有强大的心脏保护作用。然而，血管尿皮质素的调控和功能尚不清楚。方法和结果：免疫组化结果显示，在解剖心脏的冠状动脉和微血管内皮细胞中，尿皮质素有明确的表达。RT-PCR证实了尿皮质素在人脐静脉内皮细胞（HUVECs）中的表达。尿皮质素（10(-8)M）能有效抑制HUVECs中血管紧张素ii诱导的活性氧（ROS）的产生。肿瘤坏死因子α和干扰素γ增加了HUVECs中尿皮质素mRNA水平及其释放。匹伐他汀（0.1 ~ 3.0 μ M）可显著提高HUVECs尿皮质素mRNA水平和释放量。此外，使用匹伐他汀（2mg /天）治疗4周后，健康志愿者血清尿皮质素水平从11.0 +/- 6.5增加到16.4 +/- 7.3 ng/ml。结论：炎性细胞因子和匹伐他汀可上调内皮细胞尿皮质素，抑制内皮细胞ROS的产生。吡伐他汀治疗可提高受试者血清尿皮质素水平。因此，内皮尿皮质素可能在炎症病变中保护心肌细胞。尿皮质素可能部分解释了他汀类药物多种多效作用的机制。版权所有(C) 2006 S. Karger AG，巴塞尔
Background: Urocortin, a neuropeptide discovered in the midbrain, is a member of the corticotropin-releasing factor family and is expressed in heart tissues. Urocortin exerts potent cardioprotective effects under various pathological conditions including ischemia/reperfusion. However, the regulation and function of vascular urocortin are unknown. Methods and Results: Immunohistochemistry showed definitive expression of urocortin in endothelial cells of coronary large arteries and microvessels from autopsied hearts. RT-PCR confirmed the expression of urocortin in human umbilical vein endothelial cells (HUVECs). Urocortin (10(-8) M) potently sup pressed the generation of angiotensin II-induced reactive oxygen species (ROS) in HUVECs. Tumor necrosis factor alpha and interferon-gamma increased the urocortin mRNA levels and its release from HUVECs. Incubation with pitavastatin (0.1 - 3.0 mu M) significantly increased the urocortin mRNA levels and its release from HUVECs. Furthermore, treatment with pitavastatin ( 2 mg/day) for 4 weeks increased the serum urocortin level from 11.0 +/- 6.5 to 16.4 +/- 7.3 ng/ml in healthy volunteers. Conclusion: Endothelial urocortin was upregulated by inflammatory cytokines and pitavastatin and suppressed ROS production in endothelial cells. Treatment with pitavastatin increased the serum urocortin level in human subjects. Thus, endothelial urocortin might protect cardiomyocytes in inflammatory lesions. Urocortin might partly explain the mechanisms of various pleiotropic effects of statins. Copyright (C) 2006 S. Karger AG, Basel.