Modulating role of estradiol on arginase II expression in hyperlipidemic rabbits as an atheroprotective mechanism
Modulating role of estradiol on arginase II expression in hyperlipidemic rabbits as an atheroprotective mechanism
复制标题
DOI：
10.1073/pnas.0603918103
复制
发表时间：
2006-07-05
影响因子：
11.1
通讯作者：
Chaudhuri, Gautam
中科院分区：
文献类型：
--
作者：
Hayashi, Toshio;Esaki, Teiji;Chaudhuri, Gautam
我们评估了0.5%胆固醇强化饮食（HCD）对一氧化氮合酶（NOS）和NOS表达的影响以及17 β-雌二醇（E-2）对这一现象的调节作用。将30只去势兔随机分为3组，治疗15周。组I接受正常饲料;组II，HCD;组III，HCD加E-2颗粒。组II中的动物显示出血脂增加，并且它们表现出动脉粥样硬化病变以及血管内皮细胞和内膜肌细胞中伴随有大量BrdU阳性细胞的血管内皮酶I和II的表达，表明细胞增殖增加。诱导型一氧化氮合酶表达明显，硝基酪氨酸阳性区域染色增强。在第I组动物中未观察到这些情况。在这两组中，E-2水平都很低。在第III组动物中，E-2补充导致动脉粥样硬化病变和BrdU阳性细胞减少，诱导型NOS和NOS I和11的表达减少，同时伴有硝基酪氨酸染色减少。E2水平升高。我们的研究结果表明，E-2是负责这些影响，尽管动物是高血脂，类似于那些在组II。由于辅酶Ⅱ酶通过将L-精氨酸转化为多胺而负责细胞增殖，因此我们的结果表明辅酶Ⅱ酶的表达可能在动脉粥样硬化的细胞增殖中起重要作用，并且E-2抑制辅酶Ⅱ酶表达可能是减轻动脉粥样硬化形成的另一个潜在机制。
We evaluated the effects of a 0.5% cholesterol-enriched diet (HCD) on nitric-oxide synthase (NOS) and arginase expression and the modulating role of 17 beta-estradiol (E-2) on this phenomenon. Thirty oopherectomized rabbits were divided into three groups and treated for 15 weeks. Group I received normal chow; group II, HCD; and group III, HCD plus E-2 pellets. Animals in group II showed an increase in plasma lipids, and they demonstrated atheromatous lesions as well as expression of arginase I and II accompanied by a significant number of BrdU-positive cells in endothelial cells and intimal muscle cells, suggestive of an increase in cellular proliferation. There was significant expression of inducible NOS and increased staining of nitrotyrosine-positive areas. These were not observed in group I animals. In both groups, E-2 levels were low. In group III animals, E-2 supplementation led to a decrease in atheromatous lesions and BrdU-positive cells and reduced expression of both inducible NOS and arginase I and 11 accompanied by a decrease in nitrotyrosine staining. E2 levels were increased. Our results suggest that E-2 was responsible for these effects, despite the animals being hyperlipidemic, similar to those in group II. Because arginase is responsible for cell proliferation by converting L-arginine to polyamines, our results indicate that expression of arginase may play an important role in cellular proliferation in atherosclerosis, and inhibition of arginase expression by E-2 may be another potential mechanism in attenuating atherogenesis.