Angiotensin-converting enzyme 2 is an essential regulator of heart function
- PMID: 12075344
- DOI: 10.1038/nature00786
Angiotensin-converting enzyme 2 is an essential regulator of heart function
Abstract
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.
Comment in
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Two ACEs and a heart.Nature. 2002 Jun 20;417(6891):799-802. doi: 10.1038/417799a. Nature. 2002. PMID: 12075331 No abstract available.
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