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首页> 外文期刊>Endothelium: Journal of endothelial cell research >Endothelium-dependent vasorelaxation in the aorta of transgenic mice expressing human apolipoprotein(a) or lipoprotein(a).
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Endothelium-dependent vasorelaxation in the aorta of transgenic mice expressing human apolipoprotein(a) or lipoprotein(a).

机译：表达人载脂蛋白（a）或脂蛋白（a）的转基因小鼠主动脉中的内皮依赖性血管舒张。

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摘要

Elevated plasma level of lipoprotein(a) (Lp(a)) is a well established risk factor for premature atherosclerosis and coronary artery disease. Recent studies showed impaired endothelium-dependent vasodilatation in humans with elevated plasma Lp(a). However, these human studies could not determine whether (1) elevated Lp(a) levels alone are the cause of endothelial dysfunction (these patients had multiple risk factors), and (2) native or oxidatively modified Lp(a) contributes to endothelial dysfunction (no measurements of native/oxidized Lp(a) ratio was reported in humans). In order to test whether apo(a) (an essential component of Lp(a) which is required for binding to endothelial cells) and native Lp(a) cause endothelial dysfunction, in the present study we tested endothelium-dependent vasorelaxation in aortic rings isolated from control and transgenic male mice either expressing the human apo(a) gene (TgA) or both the human apo(a) and human apo B100 genes (TgL). The TgA mice had plasma apo(a) levels of 8.8 +/- 1.2 mg/dl (n=6) and the double transgenic TgL mice had plasma Lp(a) levels of 15.3 +/- 1.4 mg/dl (n=8). Isolated aortic rings with and without endothelium were mounted in organ chambers and contracted with U46619 (10(-8) M) in the presence of ibuprofen (10(-5) M). Acetylcholine caused concentration-dependent (10(-9)-10(-5) M) relaxation, which could be prevented by endothelium removal and by NG-L-nitro-arginine (10(-4) M). Basal and acetylcholine-stimulated endothelium-dependent relaxation and endothelium-independent relaxation to nitroglycerin (10(-6) M) were not significantly different in aortic rings isolated from control and TgA or TgL mice. Twenty-four hour incubation of aortic rings isolated from control mice with recombinant human apo(a) or native Lp(a) (up to 300 microg/ml) caused no impairment of endothelium-dependent relaxations. In contrast, incubation with oxidized Lp(a) (50 microg/ml) or oxidized LDL (250 microg/ml) caused significant suppression of acetylcholine-induced endothelium-dependent vasorelaxation. These results show for the first time that elevated plasma levels of apo(a) and Lp(a) do not cause endothelial dysfunction in transgenic mice.
机译：血浆脂蛋白（a）（Lp（a））水平升高是早发性动脉粥样硬化和冠状动脉疾病的公认危险因素。最近的研究表明血浆Lp（a）升高的人的内皮依赖性血管舒张功能受损。但是，这些人体研究无法确定（1）仅Lp（a）水平升高是否是内皮功能障碍的原因（这些患者有多种危险因素），以及（2）天然或氧化修饰的Lp（a）导致内皮功能障碍（未报告人类中天然/氧化的Lp（a）比的测量值）。为了测试apo（a）（与内皮细胞结合所必需的Lp（a）的基本成分）和天然Lp（a）是否引起内皮功能障碍，在本研究中，我们测试了主动脉环中的内皮依赖性血管舒张分离自表达人apo（a）基因（TgA）或人apo（a）和人apo B100基因（TgL）的对照和转基因雄性小鼠。 TgA小鼠的血浆apo（a）水平为8.8 +/- 1.2 mg / dl（n = 6），双转基因TgL小鼠的血浆Lp（a）水平为15.3 +/- 1.4 mg / dl（n = 8） ）。在有布洛芬（10（-5）M）的情况下，将有和没有内皮的孤立主动脉环安装在器官室内，并与U46619（10（-8）M）收缩。乙酰胆碱引起浓度依赖性（10（-9）-10（-5）M）松弛，可通过去除内皮和NG-L-硝基精氨酸（10（-4）M）来防止。基底和乙酰胆碱刺激的内皮依赖性舒张和对硝酸甘油（10（-6）M）的内皮依赖性舒张在从对照和TgA或TgL小鼠中分离出的主动脉环中无显着差异。从对照小鼠中分离的主动脉环与重组人apo（a）或天然Lp（a）（最高300 microg / ml）孵育二十四小时不会损害内皮依赖性舒张功能。相反，与氧化的Lp（a）（50微克/毫升）或氧化的低密度脂蛋白（250微克/毫升）孵育会显着抑制乙酰胆碱诱导的内皮依赖性血管舒张。这些结果首次表明，血浆高水平的apo（a）和Lp（a）不会在转基因小鼠中引起内皮功能障碍。

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