Tikellis Christos, Johnston Colin I, Forbes Josephine M, Burns Wendy C, Burrell Louise M, Risvanis John, Cooper Mark E
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Melbourne, Australia.
Hypertension. 2003 Mar;41(3):392-7. doi: 10.1161/01.HYP.0000060689.38912.CB. Epub 2003 Feb 24.
ACE2, initially cloned from a human heart, is a recently described homologue of angiotensin-converting enzyme (ACE) but contains only a single enzymatic site that catalyzes the cleavage of angiotensin I to angiotensin 1-9 [Ang(1-9)] and is not inhibited by classic ACE inhibitors. It also converts angiotensin II to Ang(1-7). Although the role of ACE2 in the regulation of the renin-angiotensin system is not known, the renin-angiotensin system has been implicated in the pathogenesis of diabetic complications and in particular in diabetic nephropathy. Therefore, the aim of this study was to assess the possible involvement of this new enzyme in the kidney from diabetic Sprague-Dawley rats to compare and contrast it to ACE. ACE2 and ACE gene and protein expression were measured in the kidney after 24 weeks of streptozocin diabetes. ACE2 and ACE mRNA levels were decreased in diabetic renal tubules by approximately 50% and were not influenced by ACE inhibitor treatment with ramipril. By immunostaining, both ACE2 and ACE protein were localized predominantly to renal tubules. In the diabetic kidney, there was reduced ACE2 protein expression that was prevented by ACE inhibitor therapy. The identification of ACE2 in the kidney, its modulation in diabetes, and the recent description that this enzyme plays a biological role in the generation and degradation of various angiotensin peptides provides a rationale to further explore the role of this enzyme in various pathophysiological states including diabetic complications.
血管紧张素转换酶2（ACE2）最初是从人心脏中克隆出来的，是最近发现的血管紧张素转换酶（ACE）的同源物，但仅含有一个催化血管紧张素I裂解为血管紧张素1-9 [Ang(1-9)]的酶位点，且不受经典ACE抑制剂的抑制。它还能将血管紧张素II转化为Ang(1-7)。尽管ACE2在肾素-血管紧张素系统调节中的作用尚不清楚，但肾素-血管紧张素系统已被认为与糖尿病并发症的发病机制有关，尤其是糖尿病肾病。因此，本研究的目的是评估这种新酶在糖尿病Sprague-Dawley大鼠肾脏中的可能作用，并将其与ACE进行比较和对比。在链脲佐菌素诱导糖尿病24周后，检测肾脏中ACE2和ACE的基因及蛋白表达。糖尿病肾小管中ACE2和ACE的mRNA水平降低了约50%，且不受雷米普利ACE抑制剂治疗的影响。通过免疫染色，ACE2和ACE蛋白主要定位于肾小管。在糖尿病肾脏中，ACE2蛋白表达降低，但ACE抑制剂治疗可预防这种降低。肾脏中ACE2的鉴定、其在糖尿病中的调节以及最近关于该酶在各种血管紧张素肽生成和降解中发挥生物学作用的描述，为进一步探索该酶在包括糖尿病并发症在内的各种病理生理状态中的作用提供了理论依据。
