Lu Hong, Rateri Debra L, Cassis Lisa A, Daugherty Alan
Graduate Center for Nutritional Sciences, Wethington Building, Room 521b, 900 South Limestone Street, University of Kentucky, Lexington, KY 40536-0200, USA.
Curr Hypertens Rep. 2008 Apr;10(2):99-106. doi: 10.1007/s11906-008-0020-3.
The renin-angiotensin system has been invoked in the development of both abdominal and thoracic aortic aneurysms. This has been demonstrated experimentally by the chronic subcutaneous infusion of angiotensin II, which consistently leads to development of abdominal aortic aneurysms (AAAs) in mice. Angiotensin II-induced AAAs have highly heterogenous cellular and extracellular matrix characteristics throughout the aorta that change markedly with infusion duration. The mechanistic basis for the reproducible location of AAA development has not been elucidated, but many insights have been provided, especially regarding receptor and inflammatory mechanisms. A recent clinical study provided limited evidence for extrapolating these results to mechanisms of human AAAs. Experimental evidence has also demonstrated that antagonism of angiotensin II type 1 (AT1) receptors prevents ascending aortic aneurysms in a murine model of Marfan's syndrome. A clinical study is currently ongoing to demonstrate the efficacy of AT1 receptor antagonism in humans.
肾素-血管紧张素系统已被认为与腹主动脉瘤和胸主动脉瘤的发生发展有关。通过慢性皮下输注血管紧张素II在实验中已证实了这一点，这种输注持续导致小鼠腹主动脉瘤（AAA）的形成。血管紧张素II诱导的AAA在整个主动脉中具有高度异质性的细胞和细胞外基质特征，且这些特征会随着输注持续时间而发生显著变化。AAA发生的可重复性位置的机制基础尚未阐明，但已提供了许多见解，尤其是关于受体和炎症机制方面。最近一项临床研究为将这些结果外推至人类AAA的机制提供了有限的证据。实验证据还表明，在马凡综合征的小鼠模型中，血管紧张素II 1型（AT1）受体拮抗剂可预防升主动脉瘤。目前正在进行一项临床研究以证明AT1受体拮抗剂在人类中的疗效。
