Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats
Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats
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DOI：
10.1113/expphysiol.2005.031096
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发表时间：
2005-09-01
影响因子：
2.7
通讯作者：
Raizada, MK
中科院分区：
文献类型：
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作者：
Huentelman, MJ;Grobe, JL;Raizada, MK
血管紧张素转换酶2（ACE 2）是新近发现的肾素-血管紧张素系统（RAS）的成员，由于其在血管紧张素II形成血管保护肽中的关键作用，是控制心血管疾病的潜在治疗靶点。本研究的目的是评估ACE 2过表达是否可以保护心脏免受血管紧张素II诱导的肥大和纤维化。将编码小鼠ACE 2（lenti-mACE 2）或GFP的慢病毒载体注射到5天大的Sprague-Dawley大鼠的心内。这导致在研究期间心脏组织中表达mACE 2。连续4周输注200 ng kg（-1）min（-1）血管紧张素II导致对照组大鼠收缩压升高80 mmHg，心脏重量与体重比（HW：BW）显著增加，心肌纤维化明显。用lenti-mACE 2转导导致血管紧张素II输注诱导的HW：BW增加和心肌纤维化显著减弱。这些观察结果表明，ACE 2过表达对血管紧张素II诱导的心脏肥大和纤维化具有保护作用。
Angiotensin converting enzyme 2 (ACE2), a newly discovered member of the renin-angiotensin system (RAS), is a potential therapeutic target for the control of cardiovascular disease owing to its key role in the formation of vasoprotective peptides from angiotensin II. The aim of the present study was to evaluate whether overexpression of ACE2 could protect the heart from angiotensin II-induced hypertrophy and fibrosis. Lentiviral vector encoding mouse ACE2 (lenti-mACE2) or GFP was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in expression of mACE2 in cardiac tissue for the duration of the study. Infusion of 200 ng kg(-1) min(-1) angiotensin II for 4 weeks resulted in an 80 mmHg increase in systolic blood pressure, a significant increase in the heart weight to body weight ratio (HW : BW), and marked myocardial fibrosis in control rats. Transduction with lenti-mACE2 resulted in significant attenuation of the increased HW : BW and myocardial fibrosis induced by angiotensin II infusion. These observations demonstrate that ACE2 overexpression results in protective effects on angiotensin II-induced cardiac hypertrophy and fibrosis.