Qin Zhenyu
Division of Cardiovascular Disease, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, United States.
Regul Pept. 2008 Oct 9;150(1-3):1-6. doi: 10.1016/j.regpep.2008.05.002. Epub 2008 May 14.
Angiotensin II is a major vasoactive peptide in the renin-angiotensin system (RAS). In vitro evidence demonstrates that this peptide can modulate the function of various adhesion molecules, chemokines, cytokines and growth factors, and ultimately contributes to cell proliferation, hypertrophy and inflammation. Moreover, in vivo studies further support that angiotensin II induces several vascular alterations including sustained elevations of blood pressure, enhanced inflammatory response, increased medial thickness of the aortas, and formation of aortic dissection and aneurysms. Thus, it has been a long time that angiotensin II-induced hypertension, atherosclerosis and abdominal aortic aneurysms emerge as important experimental models with respect to vascular biology. Applications of these models to investigate the vascular diseases have dramatically improved our understanding in the pathogenesis of these diseases. However, the pathophysiology of angiotensin II in vivo remains to be determined in many other vascular diseases where angiotensin II has been implicated as the detrimental factor, at least in part due to the limit availability of animal models. Recently some new exciting experimental models based on angiotensin II infusion have been reported to replicate the human diseases, such as postmenopausal hypertension, preeclampsia, vascular remodeling, vascular aging and neovascularization. In this review, we will focus on the rationales and anticipated applications of these newly developed models, with special emphasis placed on those relevant to the vascular biology. We will also discuss the limitations of the method of chronic angiotensin II infusion and additional approaches to overcome these limitations. These experimental models will provide great opportunity for us to investigate the molecular mechanisms of angiotensin II and evaluate therapeutic approaches, particularly to finely tune the potential role of RAS activation in various vascular events using genetically engineered mice.
血管紧张素II是肾素-血管紧张素系统（RAS）中的一种主要血管活性肽。体外证据表明，这种肽可以调节多种黏附分子、趋化因子、细胞因子和生长因子的功能，并最终促进细胞增殖、肥大和炎症反应。此外，体内研究进一步支持血管紧张素II可引起多种血管改变，包括血压持续升高、炎症反应增强、主动脉中层厚度增加以及主动脉夹层和动脉瘤的形成。因此，很长一段时间以来，血管紧张素II诱导的高血压、动脉粥样硬化和腹主动脉瘤已成为血管生物学方面重要的实验模型。应用这些模型来研究血管疾病极大地提高了我们对这些疾病发病机制的理解。然而，在许多其他血管疾病中，血管紧张素II在体内的病理生理学仍有待确定，在这些疾病中血管紧张素II至少部分被认为是有害因素，这至少部分是由于动物模型的可用性有限。最近，一些基于血管紧张素II输注的令人兴奋的新实验模型已被报道可复制人类疾病，如绝经后高血压、先兆子痫、血管重塑、血管老化和新生血管形成。在这篇综述中，我们将重点关注这些新开发模型的原理和预期应用，特别强调与血管生物学相关的那些。我们还将讨论慢性血管紧张素II输注方法的局限性以及克服这些局限性的其他方法。这些实验模型将为我们研究血管紧张素II的分子机制和评估治疗方法提供绝佳机会，特别是利用基因工程小鼠来精确调节RAS激活在各种血管事件中的潜在作用。
