Erythropoietin increases expression and function of vascular copper- and zinc-containing superoxide dismutase.
Erythropoietin increases expression and function of vascular copper- and zinc-containing superoxide dismutase.
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DOI：
10.1161/hypertensionaha.110.150623
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Katusic ZS
中科院分区：
文献类型：
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作者：
d'Uscio LV;Smith LA;Katusic ZS
先前的研究表明，促红细胞生成素（EPO）治疗具有血管保护作用。造成这些影响的确切机制尚不完全清楚。在本研究中，我们假设 EPO 刺激 CuZn 超氧化物歧化酶 (SOD1) 的表达和活性，从而保护血管组织免受超氧阴离子浓度过高引起的氧化应激。 EPO 治疗野生型小鼠两周（1000 U/kg，皮下注射，每两周一次）显着增加了 SOD1 的主动脉表达。这种效应导致接受治疗的小鼠主动脉中超氧阴离子浓度显着降低。 SOD1 缺陷小鼠中，EPO 减少血管产生超氧阴离子的能力被消除。在导线诱导颈总动脉损伤的小鼠模型中，用 EPO 治疗野生型小鼠可防止病理重塑，而在 SOD1 缺陷小鼠中则不存在 EPO 的血管效应。我们的研究结果表明，EPO 治疗可增加 SOD1 的血管表达。这种效应似乎是 EPO 保护血管的重要分子机制。
Previous studies have shown that treatment with erythropoietin (EPO) exerts vascular protective effects. The exact mechanisms responsible for these effects are not completely understood. In the present study we hypothesized that EPO stimulates expression and activity of CuZn-superoxide dismutase (SOD1) thus protecting vascular tissue from oxidative stress induced by excessive concentrations of superoxide anions. EPO treatment of wild type mice for two weeks (1000 U/kg, s.c., biweekly) significantly increased aortic expression of SOD1. This effect resulted in significant reduction of superoxide anion concentrations in aorta of treated mice. The ability of EPO to reduce vascular production of superoxide anions was abolished in SOD1-deficient mice. In mouse model of wire-induced injury of common carotid artery, treatment of wild-type mice with EPO prevented pathological remodeling whereas the vascular effect of EPO was absent in SOD1-deficient mice. Our findings demonstrate that treatment with EPO increases vascular expression of SOD1. This effect appears to be an important molecular mechanism underlying vascular protection by EPO.