Lack of glutathione peroxidase 1 accelerates cardiac-specific hypertrophy and dysfunction in angiotensin II hypertension.
Lack of glutathione peroxidase 1 accelerates cardiac-specific hypertrophy and dysfunction in angiotensin II hypertension.
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DOI：
10.1161/hypertensionaha.109.135715
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发表时间：
2010-01
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影响因子：
--
通讯作者：
Pagano PJ
中科院分区：
文献类型：
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作者：
Ardanaz N;Yang XP;Cifuentes ME;Haurani MJ;Jackson KW;Liao TD;Carretero OA;Pagano PJ
谷胱甘肽过氧化物酶-1通过将过氧化氢(H_2O_2)和有机氢过氧化物转化为非反应性产物而在细胞防御中发挥重要作用，而谷胱甘肽过氧化物酶活性降低的谷胱甘肽过氧化物酶-1−/−小鼠则表现出氧化应激的增强。过氧化物质参与了组织损伤和培养细胞的肥大，但GPX1在预防心血管组织终末器官损伤方面的作用尚不清楚。我们推测，GPX1缺失会增强血管紧张素II(AngII)引起的主动脉和心肌肥厚以及平均动脉压(MABP)。我们的结果表明，与野生型动物相比，短期血管紧张素转换酶抑制剂显著增加了GPX1−/−小鼠的左心室质量、心肌细胞横截面积和室间隔厚度，并降低了短轴缩短率。另一方面，在野生型和GPX1−/−小鼠中，AngII导致了类似的MABP增加。对Angii的反应增加了胶原沉积，但不同菌株之间没有发现差异。−/−小鼠和野生型小鼠血管肥大程度相同。综上所述，我们的结果表明，GPX1缺乏会加速心肌肥大和功能障碍，但对血管肥厚和MABP没有影响，并提示GPX1在血管依赖性高血压的心功能障碍中起主要作用。
Glutathione peroxidase-1 (Gpx1) plays an important role in cellular defense by converting hydrogen peroxide (H2O2) and organic hydroperoxides to non-reactive products and Gpx1−/− mice, which are characterized by reduced tissue glutathione peroxidase activity, are known to exhibit enhanced oxidative stress. Peroxides participate in tissue injury as well as the hypertrophy of cultured cells, yet the role of Gpx1 to prevent end organ damage in cardiovascular tissue is not clear. We postulated that Gpx1 deletion would potentiate both aortic and cardiac hypertrophy as well as mean arterial blood pressure (MABP) in response to angiotensin II (AngII). Our results show that short-term AngII markedly increased left ventricular mass, myocyte cross-sectional area and interventricular septum thickness and decreased shortening fraction in Gpx1−/− mice as compared to wildtype animals. On the other hand, AngII resulted in a similar increase in MABP in wildtype and Gpx1−/− mice. Collagen deposition increased in response to AngII but no differences were found between strains. Vascular hypertrophy increased to the same extent in Gpx1−/− and wildtype mice. Collectively, our results indicate that Gpx1 deficiency accelerates cardiac hypertrophy and dysfunction, but has no effect on vascular hypertrophy and MABP, and suggest a major role of Gpx1 in cardiac dysfunction in AngII-dependent hypertension.