Velkoska Elena, Patel Sheila K, Burrell Louise M
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Curr Opin Nephrol Hypertens. 2016 Sep;25(5):384-95. doi: 10.1097/MNH.0000000000000254.
Angiotensin converting enzyme 2 (ACE2) is an important regulator of the renin-angiotensin system through actions to degrade angiotensin II. Loss of ACE2 can contribute to the development and progression of cardiovascular disease, and experimental studies have highlighted a beneficial role for novel therapeutic approaches that activate or replenish tissue ACE2. This review focuses on experimental studies that have used the off-target effects of the antitrypanosomal agent, diminazene aceturate (DIZE) to activate ACE2.
In cardiovascular disease, activation of the classical renin-angiotensin system and depletion of ACE2 leads to pathophysiological changes. One approach to activate ACE2 involves the drug DIZE, which has been shown to have beneficial effects in experimental models of hypertension, pulmonary hypertension, myocardial infarction, stroke, atherosclerosis, type 1 diabetes, and eye disease. The precise mechanism of action of DIZE to activate ACE2 remains under scrutiny.
Activation of ACE2 may represent an important therapeutic approach in cardiovascular disease. To date, most studies have focused on the off-target actions of DIZE, in experimental models of disease. More research is required to determine the exact mechanism of action of DIZE and evaluate its therapeutic potential in comparison with currently available clinical interventions. There are no clinical studies of DIZE, and its side-effects, and toxicity make such studies unlikely. Hence, new methods of selectively activating or replenishing ACE2 will be needed in the future if this approach is to be used in a clinical context.
血管紧张素转换酶2（ACE2）是肾素-血管紧张素系统的重要调节因子，通过降解血管紧张素II发挥作用。ACE2的缺失会促进心血管疾病的发生和发展，实验研究突出了激活或补充组织ACE2的新型治疗方法的有益作用。本综述聚焦于利用抗锥虫药乙酰氨基阿维菌素（DIZE）的脱靶效应激活ACE2的实验研究。
在心血管疾病中，经典肾素-血管紧张素系统的激活和ACE2的耗竭会导致病理生理变化。激活ACE2的一种方法涉及药物DIZE，已证明其在高血压、肺动脉高压、心肌梗死、中风、动脉粥样硬化、1型糖尿病和眼病的实验模型中具有有益作用。DIZE激活ACE2的确切作用机制仍在研究中。
激活ACE2可能是心血管疾病的一种重要治疗方法。迄今为止，大多数研究都集中在疾病实验模型中DIZE的脱靶作用上。需要更多研究来确定DIZE的确切作用机制，并与目前可用的临床干预措施相比评估其治疗潜力。目前尚无关于DIZE的临床研究，其副作用和毒性使得此类研究不太可能进行。因此，如果要在临床环境中使用这种方法，未来将需要选择性激活或补充ACE2的新方法。
