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首页> 外文期刊>Journal of Lipid Research >Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins.
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Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins.

机译:动脉粥样硬化小鼠中内皮素转化酶1的增加:氧化的低密度脂蛋白的潜在作用。

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摘要

The aim of our study was to analyze the relationships between atherosclerosis and endothelin-converting enzyme-1 (ECE-1). Four-week-old C57BL/6J [wild-type (WT)] and apolipoprotein E-deficient (apoE) mice were fed with a standard or Western-type fat diet for 8 wks. ApoE showed atherosclerotic lesions in the aorta, higher blood pressure and vascular lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) protein content than WT. ApoE showed a significant increase in ECE-1 protein content and mRNA expression in aorta, lung, and kidney, without changes in heart. When an ECE-1 inhibitor, FR-901533, was administered to them, blood pressure decreased in apoE on fat diet versus apoE on normal diet and WT. ECE-1 and LOX-1 protein content were elevated in peripheral blood mononuclear cells (PBMC) from hypercholesterolemic patients. In order to study the mechanism involved in this ECE-1 up-regulation, bovine aortic endothelial cells (BAEC) were treated with oxidized-low density lipoproteins (oxLDL). OxLDL, but not LDL, increased ECE-1 protein content, mRNA expression and promoter activity. Our results demonstrate that ECE-1 increases in different atherosclerosis situations. Up-regulation of ECE-1 could contribute, at least partially, to the development of hypertension seen in apoE mice, because FR-901533 avoided it. Probably, atherosclerotic situations course with an increase of oxLDL, which is able to induce ECE-1 expression with the subsequent potential pathological effects.
机译:我们研究的目的是分析动脉粥样硬化与内皮素转化酶-1(ECE-1)之间的关系。给四周大的C57BL / 6J [野生型(WT)]和载脂蛋白E缺乏症(apoE)小鼠喂食标准或西式脂肪饮食8周。与WT相比,ApoE在主动脉中显示出动脉粥样硬化病变,较高的血压和血管凝集素样氧化的低密度脂蛋白受体1(LOX-1)蛋白含量。 ApoE在主动脉,肺和肾脏中的ECE-1蛋白含量和mRNA表达显着增加,而心脏没有变化。当给他们服用ECE-1抑制剂FR-901533时,脂肪饮食的apoE血压下降,而正常饮食和WT的apoE血压下降。高胆固醇血症患者外周血单个核细胞(PBMC)中的ECE-1和LOX-1蛋白含量升高。为了研究这种ECE-1上调的机制,用氧化低密度脂蛋白(oxLDL)处理了牛主动脉内皮细胞(BAEC)。 OxLDL(而非LDL)增加了ECE-1蛋白含量,mRNA表达和启动子活性。我们的结果表明,ECE-1在不同的动脉粥样硬化情况下会增加。 EFR-1的上调至少可以部分导致apoE小鼠高血压的发生,因为FR-901533避免了它的发生。可能随着oxLDL的增加而发生动脉粥样硬化,这种情况能够诱导ECE-1表达并带来潜在的病理影响。

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