Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension
Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension
复制标题
DOI：
10.1016/s0008-6363(97)00049-7
复制
发表时间：
1997-05-01
影响因子：
10.8
通讯作者：
Stenmark, KR
中科院分区：
文献类型：
--
作者：
Morrell, NW;Danilov, SM;Stenmark, KR
目的：确定缺氧诱导右心室肥厚过程中局部心脏血管紧张素转换酶（ACE）表达是否上调。研究方法：ACE活性测定膜制剂从右心室和左心室加上隔膜在常氧大鼠和动物暴露于慢性缺氧8和14天。使用ACE单克隆抗体（9B9）通过免疫组织化学研究局部心脏ACE表达。结果如下：在正常大鼠心脏中，ACE表达仅限于血管内皮、瓣膜内皮和壁内皮的局部区域。我们发现，肺动脉高压和右心室肥大的发展与缺氧8天和14天的膜结合右心室ACE活性分别增加2.6倍和3.4倍有关。右室ACE活性与右室肥厚程度呈正相关（r = 0.83，P < 0.001）。与此相反，左心室加间隔ACE活性显着减少约40和60%，分别由缺氧8和14天，与对照组相比。在慢性缺氧大鼠右心室，免疫组化显示心肌纤维化区域ACE表达增加。有趣的是，慢性缺氧大鼠右心室心外膜ACE表达增加。在左心室游离壁，慢性缺氧大鼠表达ACE的心肌毛细血管数量明显减少。总结：慢性缺氧对左心室和右心室ACE活性有不同的影响，并且ACE表达改变的部位高度定位。我们推测局部增加的右心室ACE活性和表达可能在继发于缺氧性肺动脉高压的右心室肥大的发病机制中发挥作用。
Objective: To determine whether local cardiac angiotensin converting enzyme (ACE) expression is upregulated during the development of hypoxia-induced right ventricular hypertrophy. Methods: ACE activity was measured in membrane preparations from the right ventricle and left ventricle plus septum in normoxic rats and animals exposed to chronic hypoxia for 8 and 14 days. Local cardiac ACE expression was studied by immunohistochemistry using a monoclonal antibody to ACE (9B9). Results: In the normal rat heart, ACE expression was confined to vascular endothelium, the valvular endocardium, and localized regions of parietal endocardium. We found that the development of pulmonary hypertension and right ventricular hypertrophy were associated with 2.6- and 3.4-fold increases in membrane-bound right ventricular ACE activity by 8 and 14 days of hypoxia, respectively. Right ventricular ACE activity was positively correlated with the degree of right ventricular hypertrophy (r = 0.83, P < 0.001). In contrast, left ventricular plus septal ACE activity was significantly reduced by approximately 40 and 60% by 8 and 14 days of hypoxia, respectively, compared to controls. In the right ventricle of chronically hypoxic rats, immunohistochemistry demonstrated increased ACE expression in areas of myocardial fibrosis. Interestingly, increased ACE expression was noted in the right ventricular epicardium in chronically hypoxic rats. In the free wall of the left ventricle there was a significant reduction in the number of myocardial capillaries which expressed ACE in chronically hypoxic rats. Conclusion: Chronic hypoxia has a differential effect on left and right ventricular ACE activity and that the sites of altered ACE expression are highly localized. We speculate that locally increased right ventricular ACE activity and expression may play a role in the pathogenesis of right ventricular hypertrophy secondary to hypoxic pulmonary hypertension.