Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice
Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice
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DOI：
10.1172/jci7818
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发表时间：
2000-06-01
影响因子：
15.9
通讯作者：
Cassis, LA
中科院分区：
文献类型：
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作者：
Daugherty, A;Manning, MW;Cassis, LA
血管紧张素 II (Ang II) 血浆浓度升高与动脉粥样硬化形成有关。为了直接检查这种关系，我们通过渗透微型泵将 Ang II 或媒介物注入成熟的 apoE(-/-) 小鼠体内 1 个月。这些剂量的 Ang LI 不会改变动脉血压、体重、血清胆固醇浓度或脂蛋白胆固醇的分布。然而，Ang II 输注会加剧主动脉粥样硬化病变的严重程度。这些 Ang II 诱导的病变主要是富含脂质的巨噬细胞和淋巴细胞；此外，Ang II 促进病变下外膜组织中巨噬细胞数量显着增加。出乎意料的是，注射Ang II 的apoE(-/-) 小鼠中出现了明显的腹主动脉瘤。动脉瘤腹主动脉的连续切片显示了两个主要特征：被大的重塑的外膜包围的完整动脉，以及具有明显扩张和更适度重塑的外膜组织的内侧断裂。尽管在内侧断点处没有看到动脉粥样硬化病变，但需要存在高脂血症，因为将Ang II输注到apoE(+/+)小鼠体内未能产生动脉瘤。这些结果表明，在没有血流动力学影响的情况下，当与高脂血症结合时，Ang II 血浆浓度的增加对血管病理学具有深远而快速的影响。
Increased plasma concentrations of angiotension II (Ang II) have been implicated in atherogenesis. To examine this relationship directly, we infused Ang II or vehicle for 1 month via osmotic minipumps into mature apoE(-/-) mice. These doses of Ang LI did not alter arterial blood pressure, body weight, serum cholesterol concentrations, or distribution of lipoprotein cholesterol. However, Ang II infusions promoted an increased severity of aortic atherosclerotic lesions. These Ang II-induced lesions were predominantly lipid-laden macrophages and lymphocytes; moreover, Ang II promoted a marked increase in the number of macrophages present in the adventitial tissue underlying lesions. Unexpectedly, pronounced abdominal aortic aneurysms were present in apoE(-/-) mice infused with Ang II. Sequential sectioning of aneurysmal abdominal aorta revealed two major characteristics: an intact artery that is surrounded by a large remodeled adventitia, and a medial break with pronounced dilation and more modestly remodeled adventitial tissue. Although no atherosclerotic lesions were visible at the medial break point, the presence of hyperlipidemia was required because infusions of Ang II into apoE(+/+) mice failed to generate aneurysms. These results demonstrate that increased plasma concentrations of Ang II have profound and rapid effects on vascular pathology when combined with hyperlipidemia, in the absence of hemodynamic influences.