Myocardial infarction increases ACE2 expression in rat and humans
Myocardial infarction increases ACE2 expression in rat and humans
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心肌梗塞会增加大鼠和人类 ACE2 的表达
DOI：
10.1093/eurheartj/ehi114
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发表时间：
2005-02-01
影响因子：
39.3
通讯作者：
Johnston, CI
中科院分区：
文献类型：
--
作者：
Burrell, LM;Risvanis, J;Johnston, CI
目的 血管紧张素转换酶2（ACE2）催化血管紧张素（Ang）I裂解为Ang 1 - 9以及Ang II裂解为Ang 1 - 7。ACE2缺乏会损害心脏收缩力并上调缺氧诱导基因，提示其与心肌缺血存在关联。我们研究了大鼠心肌梗死（MI）后以及人类衰竭心脏中ACE2的表达。
方法与结果 在MI后第1、3和28天处死大鼠，或用ACE抑制剂雷米普利（1 mg/kg）治疗4周。分别通过实时定量逆转录聚合酶链反应和免疫组织化学/活性测定/体外放射自显影评估心脏中ACE和ACE2的基因及蛋白质表达。MI后第3天，与存活区域相比，边缘/梗死区域的ACE（P = 0.022）和ACE2（P = 0.015）mRNA均增加。到第28天，与对照大鼠的心肌相比，MI大鼠存活心肌中的ACE（P = 0.005）和ACE2（P = 0.006）mRNA也有所增加。ACE2蛋白定位于巨噬细胞、血管内皮、平滑肌和心肌细胞。雷米普利减轻心脏肥大并抑制心脏ACE。相反，雷米普利对心脏ACE2 mRNA无影响，其在MI大鼠心脏的所有区域仍保持升高。在衰竭的人类心脏中，ACE和ACE2的免疫反应性均增加。
结论 MI后ACE2的增加表明，它在心脏损伤后血管紧张素肽的生成和降解过程中对肾素 - 血管紧张素系统的负向调节起重要作用。
Aims Angiotensin converting enzyme (ACE) 2 catalyses the cleavage of angiotensin (Ang) I to Ang 1-9 and of Ang II to Ang 1-7. ACE2 deficiency impairs cardiac contractility and upregutates hypoxia-induced genes, suggesting a link with myocardial ischaemia. We studied the expression of ACE2 after myocardial infarction (MI) in the rat as well as in human failing hearts.Methods and results Rats were killed at days 1, 3, and 28 after MI, or treated for 4 weeks with the ACE inhibitor ramipril (1 mg/kg). Cardiac gene and protein expression of ACE and ACE2 were assessed by quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry/activity assays/in vitro autoradiography, respectively. Both ACE (P = 0.022) and ACE2 (P = 0.015) mRNA increased in the border/infarct area compared with the viable area at day 3 after MI. By day 28, increases in ACE (P = 0.005) and ACE2 (P = 0.006) mRNA were also seen in the viable myocardium of MI rats compared with myocardium of control rats. ACE2 protein localized to macrophages, vascular endothelium, smooth muscle, and myocytes. Ramipril attenuated cardiac hypertrophy and inhibited cardiac ACE. In contrast, ramipril had no effect on cardiac ACE2 mRNA, which remained elevated in all areas of the MI rat heart. Immunoreactivity of both ACE and ACE2 increased in failing human hearts.Conclusion The increase in ACE2 after MI suggests that it plays an important role in the negative modulation of the renin angiotensin system in the generation and degradation of angiotensin peptides after cardiac injury.