Detection of soluble angiotensin-converting enzyme 2 in heart failure: insights into the endogenous counter-regulatory pathway of the renin-angiotensin-aldosterone system.
Detection of soluble angiotensin-converting enzyme 2 in heart failure: insights into the endogenous counter-regulatory pathway of the renin-angiotensin-aldosterone system.
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DOI：
10.1016/j.jacc.2008.02.088
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发表时间：
2008-08-26
影响因子：
24
通讯作者：
Sen, Subha
中科院分区：
文献类型：
--
作者：
Epelman, Slava;Tang, W. H. Wilson;Chen, Stephen Y.;Van Lente, Frederick;Francis, Gary S.;Sen, Subha
我们试图确定心力衰竭(HF)患者血浆中循环可溶性血管紧张素转换酶2(SACE2)是否升高。血管紧张素转换酶2(ACE2)是一种完整的膜蛋白，在动物模型中能拮抗血管紧张素II的作用，防止心衰的发生。然而，由于有创性心脏组织采样的需要，关于ACE2是否参与人类心力衰竭的病理生理学还知之甚少。我们开发了一种灵敏而特异的方法来测量人血浆中sACE2的活性，并筛选了一组怀疑患有临床心力衰竭的患者。血浆sACE2活性的增加与心衰的临床诊断密切相关(p=0.0002)，与左心室射血分数恶化(p<；0.0001)和B型利钠肽水平升高(p<；0.0001)密切相关。与B型利钠肽相似，sACE2活性反映了心力衰竭的严重程度，随着纽约心脏协会功能分级的恶化而增加(p<；0.0001)。这些关联独立于其他疾病状态和药物使用。我们发现，在缺血性和非缺血性心肌病患者以及临床心衰但左心室射血分数保留的患者中，sACE2活性均增加。可溶性ACE2活性在心力衰竭患者中升高，并与疾病严重程度相关，提示肾素-血管紧张素-醛固酮系统的心脏保护臂在心力衰竭中是活跃的。
We sought to determine whether circulating soluble angiotensin-converting enzyme 2 (sACE2) is increased in the plasma of patients with heart failure (HF). Angiotensin-converting enzyme 2 (ACE2) is an integral membrane protein that antagonizes the actions of angiotensin II and prevents the development of HF in animal models. However, because of the need for invasive cardiac tissue sampling, little is known about whether ACE2 is involved in the pathophysiology of HF in humans. We developed a sensitive and specific assay to measure sACE2 activity in human plasma and screened a heterogeneous group of patients suspected of having clinical HF. Increasing sACE2 plasma activity strongly correlated with a clinical diagnosis of HF (p = 0.0002), worsening left ventricular ejection fraction (p < 0.0001), and increasing B-type natriuretic peptide levels (p < 0.0001). Similar to B-type natriuretic peptide, sACE2 activity reflected the severity of HF, with increasing levels associated with worsening New York Heart Association functional class (p < 0.0001). These associations were independent of other disease states and medication use. We found that sACE2 activity was increased in patients with both ischemic and nonischemic cardiomyopathies and also in patients with clinical HF but a preserved left ventricular ejection fraction. Soluble ACE2 activity is increased in patients with HF and correlates with disease severity, suggesting that a cardioprotective arm of the renin-angiotensin-aldosterone system is active in HF.
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DOI：
10.1074/jbc.m505111200
发表时间：
2005-08-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lambert DW;Yarski M;Warner FJ;Thornhill P;Parkin ET;Smith AI;Hooper NM;Turner AJ
通讯作者：
Turner AJ
影响因子：
64.8
作者：
Crackower, MA;Sarao, R;Penninger, JM
通讯作者：
Penninger, JM
影响因子：
2.7
作者：
Huentelman, MJ;Grobe, JL;Raizada, MK
通讯作者：
Raizada, MK
影响因子：
20.1
作者：
Keidar, S;Gamliel-Lazarovich, A;Abassi, Z
通讯作者：
Abassi, Z
影响因子：
4.8
作者：
Huang, LL;Sexton, DJ;Ladner, RC
通讯作者：
Ladner, RC