Pharmacologically induced thoracic and abdominal aortic aneurysms in mice.
Pharmacologically induced thoracic and abdominal aortic aneurysms in mice.
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DOI：
10.1161/hypertensionaha.109.140558
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Hashimoto T
中科院分区：
文献类型：
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作者：
Kanematsu Y;Kanematsu M;Kurihara C;Tsou TL;Nuki Y;Liang EI;Makino H;Hashimoto T
主动脉瘤在老年人群中很常见。绝大多数的主动脉瘤位于两个不同的动脉瘤易发区域-腹主动脉和胸主动脉，包括升主动脉。在这项研究中，我们结合了与人类主动脉瘤相关的两个因素-高血压和弹性膜变性-在小鼠中诱导主动脉瘤。使用（1）两种不同的诱导高血压的方法和（2）抗高血压药物评估血流动力学条件在主动脉瘤形成中的作用。在9周龄的C57 BL/6 J雄性小鼠中，通过血管紧张素II或醋酸脱氧皮质酮（DOCA）盐高血压诱导高血压;通过输注赖氨酰氧化酶抑制剂β-氨基丙腈诱导弹性膜变性。无论诱导高血压的方法如何，小鼠均发生胸主动脉瘤和腹主动脉瘤（分别为38-50%和30- 49%）。在两个动脉瘤易发区发现动脉瘤，具有部位特异性形态学和组织学特征。在接受血管紧张素II和β-氨基丙腈的小鼠中，用抗高血压药物治疗，使血压正常化，并显着减少动脉瘤形成。然而，在接受脱氧皮质酮醋酸盐和β-氨基丙腈的小鼠中，用血管紧张素转换酶抑制剂captopril治疗并不影响血压或主动脉瘤的发生率。总之，我们已经证明，高血压和药理学诱导的弹性层变性的组合可以诱导具有部位特异性特征的胸主动脉瘤和腹主动脉瘤。该模型中的动脉瘤形成依赖于高血压，但不依赖于血管紧张素II对血管壁的直接作用。
Aortic aneurysms are common among the elderly population. Large majority of aortic aneurysms are located at two distinct aneurysm-prone regions—the abdominal aorta and thoracic aorta involving the ascending aorta. In this study, we combined two factors that are associated with human aortic aneurysms—hypertension and degeneration of elastic lamina—to induce an aortic aneurysm in mice. Roles of hemodynamic conditions in the formation of aortic aneurysms were assessed using (1) two different methods for inducing hypertension, and (2) anti-hypertensive agents. In nine-week-old C57BL/6J male mice, hypertension was induced by angiotensin-II or deoxycorticosterone acetate (DOCA)-salt hypertension; degeneration of elastic lamina was induced by infusion of beta-aminopropionitrile, a lysyl oxidase inhibitor. Irrespective of the methods for inducing hypertension, mice developed thoracic and abdominal aortic aneurysms (38-50% and 30-49 %, respectively). Aneurysms were found at the two aneurysm-prone regions with site-specific morphological and histological characteristics. Treatment with anti-hypertensive agent, amlodipine, normalized blood pressure and dramatically reduced aneurysm formation in the mice that received angiotensin-II and beta-aminopropionitrile. However, a treatment with captopril, angiotensin converting enzyme inhibitor, did not affect blood pressure or the incidence of aortic aneurysms in the mice that received deoxycorticosterone acetate-salt and beta-aminopropionitrile. In summary, we have shown that a combination of hypertension and pharmacologically-induced degeneration of elastic laminas can induce both thoracic and abdominal aortic aneurysms with site-specific characteristics. The aneurysm formation in this model was dependent on hypertension, but not on direct effects of angiotensin-II to the vascular wall.