Autocrine Human Urotensin II Enhances Macrophage-Derived Foam Cell Formation in Transgenic Rabbits.

Autocrine Human Urotensin II Enhances Macrophage-Derived Foam Cell Formation in Transgenic Rabbits.
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自分泌人尾加压素 II 增强转基因兔中巨噬细胞衍生的泡沫细胞形成。

DOI:
10.1155/2015/843959
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发表时间:
2015
影响因子:
--
通讯作者:
Liu E
Liu E
中科院分区:
生物学3区
文献类型:
--
作者:
Zhao S;Li Y;Gao S;Wang X;Sun L;Cheng D;Bai L;Guan H;Wang R;Fan J;Liu E

文献摘要

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循环尾加压素II(UII)参与动脉粥样硬化的发展。然而,自分泌UII在动脉粥样硬化发展中的作用仍不清楚。在这里,我们测试的假设,自分泌UII会促进动脉粥样硬化。建立转基因兔模型,研究巨噬细胞特异性表达人UII(hUII),并用于研究自分泌UII在动脉粥样硬化发展中的作用。转基因兔子和它们的非转基因同窝出生的兔子被喂食高胆固醇饮食以诱导动脉粥样硬化。与非转基因同窝出生的转基因兔相比,观察到hUII表达使动脉粥样硬化病变中的巨噬细胞阳性面积增加了45%,转基因兔中的阳性面积比增加了56%。自分泌hUII显着降低平滑肌细胞阳性面积比转基因兔(54%),而不影响血浆总胆固醇,甘油三酯,低密度脂蛋白胆固醇,高密度脂蛋白胆固醇,葡萄糖和脂肪组织含量。这些结果首次阐明了自分泌UII通过增加巨噬细胞源性泡沫细胞的积累在动脉粥样硬化的发展中起重要作用。
Circulating urotensin II (UII) is involved in the development of atherosclerosis. However, the role of autocrine UII in the development of atherosclerosis remains unclear. Here, we tested the hypothesis that autocrine UII would promote atherosclerosis. Transgenic rabbits were created as a model to study macrophage-specific expressing human UII (hUII) and used to investigate the role of autocrine UII in the development of atherosclerosis. Transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet to induce atherosclerosis. Comparing the transgenic rabbits with their nontransgenic littermates, it was observed that hUII expression increased the macrophage-positive area in the atherosclerotic lesions by 45% and the positive area ratio by 56% in the transgenic rabbits. Autocrine hUII significantly decreased the smooth muscle cell-positive area ratio in transgenic rabbits (by 54%), without affecting the plasma levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and glucose and adipose tissue contents. These results elucidated for the first time that autocrine UII plays an important role in the development of atherosclerosis by increasing the accumulation of macrophage-derived foam cell.