Chronic angiotensin II infusion promotes atherogenesis in low density lipoprotein receptor -/- mice
Chronic angiotensin II infusion promotes atherogenesis in low density lipoprotein receptor -/- mice
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DOI：
10.1111/j.1749-6632.1999.tb07789.x
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Cassis, L
中科院分区：
文献类型：
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作者：
Daugherty, A;Cassis, L
本研究的目的是确定慢性血管紧张素IT（AngII）输注对低密度脂蛋白（LDL）受体-/-小鼠已建立病变的致动脉粥样硬化过程的严重程度的影响。LDL受体-/-小鼠接受富含胆固醇、饱和脂肪和胆酸盐的饮食，用盐水或AngII（500 ng/kg/min）输注28天。在LDL受体-/-小鼠中，血管紧张素II输注7天后，收缩压升高，随后在28天时下降至基线水平，尽管继续输注血管紧张素II。在LDL受体-/-小鼠中，血清胆固醇不受AngII输注的影响;然而，在接受AngII的LDL受体-/-小鼠中，血清甘油三酯浓度显著降低。在LDL受体-/-小鼠接受AngII治疗时，病变覆盖的内膜表面积百分比没有增加;然而，在输注AngII的小鼠中，弓、胸和腹主动脉病变中的胆固醇（酯化和未酯化）含量显著增加。值得注意的是，在20%的LDL受体-/-小鼠接受血管紧张素II，大动脉瘤被发现在腹主动脉。动脉瘤表现为血管壁的中膜和周围组织破裂，包括无定形和无细胞肿块，伴有血栓物质斑块。这些结果表明，AngII的慢性输注促进LDL受体-/-小鼠中的致动脉粥样硬化过程，表现为病变胆固醇含量的增加。AngII促进动脉粥样硬化形成的作用在不显著升高收缩压的剂量下是明显的。重要的是，在LDL受体-/-小鼠中输注AngII导致主动脉瘤的发展。
The purpose of this study was to determine the effect of chronic angiotensin IT (AngII) infusion on the severity of the atherogenic process in low density lipoprotein (LDL) receptor -/- mice with established lesions. LDL receptor -/- mice receiving a diet enriched in cholesterol, saturated fat, and cholate, were infused with saline or AngII (500 ng/kg/min) for 28 days. Systolic blood pressure increased in LDL receptor -/- mice following 7 days of AngII infusion, followed by a decline to baseline levels at 28 days, despite continued AngII infusion. Serum cholesterol was not influenced by AngII infusion In LDL receptor -/- mice; however, serum triglyceride concentrations were reduced significantly in LDL receptor -/- mice receiving AngII. The percent of intimal surface area covered by lesion was not increased in LDL receptor -/- mice receiving AngII; however, the content of cholesterol (esterified and unesterified) in lesions of the arch, thoracic, and abdominal aorta was significantly increased in those mice infused with AngII. Of note, in 20% of the LDL receptor -/- mice receiving AngII, large aneurysms were found in the abdominal aorta. Aneurysms appeared as breaks in the media and surrounding tissue of the vessel wail, encompassing amorphous and acellular masses with patches of thrombotic material. These results demonstrate that chronic infusion of AngII promotes the atherogenic processes in LDL receptor -/- mice, manifest as increases in lesion cholesterol content. Effects of AngII to promote atherogenesis mere apparent at doses which did not markedly elevate systolic pressure. Importantly, infusion of AngII: in LDL receptor -/- mice resulted in the development of aortic aneurysms.