Angiotensin-converting enzyme 2 is an essential regulator of heart function - PubMed (original) (raw)

. 2002 Jun 20;417(6891):822-8.

doi: 10.1038/nature00786.

Renu Sarao, Gavin Y Oudit, Chana Yagil, Ivona Kozieradzki, Sam E Scanga, Antonio J Oliveira-dos-Santos, Joan da Costa, Liyong Zhang, York Pei, James Scholey, Carlos M Ferrario, Armen S Manoukian, Mark C Chappell, Peter H Backx, Yoram Yagil, Josef M Penninger

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Angiotensin-converting enzyme 2 is an essential regulator of heart function

Michael A Crackower et al. Nature. 2002.

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.

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