ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis
ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis
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DOI：
10.1177/1470320314542829
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发表时间：
2015-06-01
影响因子：
2.9
通讯作者：
Dong, Bo
中科院分区：
文献类型：
--
作者：
Zhang, Yue Hui;Hao, Qing Qing;Dong, Bo
简介：血管紧张素转换酶2（ACE2）是肾素-血管紧张素系统（RAS）的新成员，有人提出ACE2是控制心血管疾病的潜在治疗靶点。研究氯沙坦对动脉粥样硬化中ACE2活性的影响。方法：采用高胆固醇饮食诱导新西兰大白兔动脉粥样硬化3个月。给予血管紧张素 II (Ang II) 受体阻滞剂（氯沙坦，25 mg/kg/d）3 个月。采用荧光法测定ACE2活性，采用H&E和油红O染色评价动脉粥样硬化程度。此外，还评估了氯沙坦对体外平滑肌细胞（SMC）中ACE2活性的影响。结果：氯沙坦增加了体内动脉粥样硬化和体外SMC中ACE2的活性。氯沙坦抑制动脉粥样硬化的演变。添加氯沙坦可阻断Ang II诱导的ACE2活性下调，而PD98059阻断细胞外信号调节激酶（ERK1/2）可阻止Ang II诱导的ACE2活性下调。结论：结果表明氯沙坦可调节动脉粥样硬化斑块中的ACE2活性，可能在动脉粥样硬化的治疗中发挥重要作用。其机制涉及Ang II-AT1R介导的丝裂原激活蛋白激酶、MAPKs(MAPKs)信号通路。
Introduction: Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied.Methods: Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated.Results: Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity.Conclusions: The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway.