Dean Rachael G, Burrell Louise M
Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3081, Victoria, Australia.
Curr Pharm Des. 2007;13(26):2730-5. doi: 10.2174/138161207781662876.
Angiotensin converting enzyme (ACE) is a key enzyme in the renin angiotensin system (RAS) and converts angiotensin (Ang) I to the vasoconstrictor Ang II, which is thought to be responsible for most of the physiological and pathophysiological effects of the RAS. This classical view of the RAS was challenged with the discovery of the enzyme, ACE2 which both degrades Ang II and leads to formation of the vasodilatory and anti-proliferative peptide, Ang 1-7. Activation of the RAS is a major contributor to diabetic complications, and blockade of the vasoconstrictor and hypertrophic actions of Ang II, slows but does not prevent the progression of such complications. The identification of ACE2 in the heart and kidney adds further complexity to the RAS, provides the rationale to explore the role of this enzyme in pathophysiological states, including the microvascular and macrovascular complications of diabetes. It is believed that ACE2 acts in a counter-regulatory manner to ACE to modulate the balance between vasoconstrictors and vasodilators within the heart and kidney, and may thus play a significant role in the pathophysiology of cardiac and renal disease. Relatively little is known about ACE2 in diabetes, and this review will explore and discuss the data that is currently available. The discovery of ACE2 presents a novel opportunity to develop drugs that specifically influence ACE2 activity and/or expression, and it is possible that such compounds may have considerable clinical value in the prevention and treatment of the complications of diabetes.
血管紧张素转换酶（ACE）是肾素血管紧张素系统（RAS）中的关键酶，可将血管紧张素（Ang）I转化为血管收缩剂Ang II，人们认为Ang II是RAS大多数生理和病理生理效应的原因。随着酶ACE2的发现，RAS的这一经典观点受到了挑战，ACE2既能降解Ang II，又能导致血管舒张和抗增殖肽Ang 1-7的形成。RAS的激活是糖尿病并发症的主要促成因素，阻断Ang II的血管收缩和肥大作用可减缓但不能阻止此类并发症的进展。心脏和肾脏中ACE2的发现使RAS更加复杂，为探索该酶在病理生理状态中的作用提供了理论依据，包括糖尿病的微血管和大血管并发症。人们认为ACE2以与ACE相反的调节方式发挥作用，以调节心脏和肾脏内血管收缩剂和血管舒张剂之间的平衡，因此可能在心脏和肾脏疾病的病理生理学中发挥重要作用。关于糖尿病中ACE2的了解相对较少，本综述将探讨和讨论目前可用的数据。ACE2的发现为开发特异性影响ACE2活性和/或表达的药物提供了新机会，此类化合物可能在糖尿病并发症的预防和治疗中具有相当大的临床价值。
