Angiotensin-converting enzyme 2 is an essential regulator of heart function
Angiotensin-converting enzyme 2 is an essential regulator of heart function
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DOI：
10.1038/nature00786
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发表时间：
2002-06-20
期刊：
影响因子：
64.8
通讯作者：
Penninger, JM
中科院分区：
文献类型：
--
作者：
Crackower, MA;Sarao, R;Penninger, JM
预计到2020年，心血管疾病将成为全世界最常见的死亡原因。在三种不同的高血压大鼠模型中，血管紧张素转换酶2 （ace2）映射到X染色体上一个定义的数量性状位点（QTL）。在所有高血压大鼠品系中，ACE2信使RNA和蛋白的表达均显著降低，表明ACE2是该QTL的候选基因。在小鼠中靶向破坏ACE2可导致严重的心脏收缩性缺陷、血管紧张素II水平升高和心脏缺氧诱导基因上调。在ACE2突变背景下，ACE基因消融完全挽救了心脏表型。但是破坏ACER（果蝇ACE2的同系物）会导致心脏形态发生的严重缺陷。这些基因数据表明ACE2是体内心脏功能的重要调节因子。
Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo.