Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice.
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice.
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DOI：
10.3791/53191
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发表时间：
2015-09-28
期刊：
影响因子：
--
通讯作者：
Daugherty A
中科院分区：
文献类型：
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作者：
Lu H;Howatt DA;Balakrishnan A;Moorleghen JJ;Rateri DL;Cassis LA;Daugherty A
渗透泵以恒定的速率将化合物持续输送到小动物体内。本文介绍了一个标准的协议，用于诱导主动脉瘤通过皮下注射血管紧张素II（AngII）植入渗透泵。该方案包括计算AngII量和溶解、渗透泵填充、皮下植入渗透泵、泵植入后观察和收获动脉瘤以可视化小鼠中的主动脉瘤。根据该方案通过渗透泵皮下输注AngII是诱导小鼠腹主动脉瘤和胸主动脉瘤的可靠且可重复的技术。根据研究目的，输注持续时间从几天到几个月不等。AngII 1，000 ng/kg/min足以对雄性高胆固醇血症小鼠模型（如载脂蛋白E缺陷或低密度脂蛋白受体缺陷小鼠）的腹主动脉瘤形成产生最大作用。通过渗透泵输注AngII诱导的腹主动脉瘤的发病率在雌性高胆固醇血症小鼠中低5 - 10倍，并且在两种性别的胆固醇正常小鼠中也较低。相反，AngII诱导的小鼠胸主动脉瘤不是高胆固醇血症或性别依赖性的。重要的是，这种小鼠模型的多个特征概括了人类主动脉瘤的特征。
Osmotic pumps continuously deliver compounds at a constant rate into small animals. This article introduces a standard protocol used to induce aortic aneurysms via subcutaneous infusion of angiotensin II (AngII) from implanted osmotic pumps. This protocol includes calculation of AngII amount and dissolution, osmotic pump filling, implantation of osmotic pumps subcutaneously, observation after pump implantation, and harvest of aortas to visualize aortic aneurysms in mice. Subcutaneous infusion of AngII through osmotic pumps following this protocol is a reliable and reproducible technique to induce both abdominal and thoracic aortic aneurysms in mice. Infusion durations range from a few days to several months based on the purpose of the study. AngII 1,000 ng/kg/min is sufficient to provide maximal effects on abdominal aortic aneurysmal formation in male hypercholesterolemic mouse models such as apolipoprotein E deficient or low-density lipoprotein receptor deficient mice. Incidence of abdominal aortic aneurysms induced by AngII infusion via osmotic pumps is 5 - 10 times lower in female hypercholesterolemic mice and also lower in both genders of normocholesterolemic mice. In contrast, AngII-induced thoracic aortic aneurysms in mice are not hypercholesterolemia or gender-dependent. Importantly, multiple features of this mouse model recapitulate those of human aortic aneurysms.