Angiotensin-converting enzyme 2 is an essential regulator of heart function |
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| Authors: | Crackower Michael A Sarao Renu Oudit Gavin Y Yagil Chana Kozieradzki Ivona Scanga Sam E Oliveira-dos-Santos Antonio J da Costa Joan Zhang Liyong Pei York Scholey James Ferrario Carlos M Manoukian Armen S Chappell Mark C Backx Peter H Yagil Yoram Penninger Josef M |
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| Institution: | Amgen Research Institute/Ontario Cancer Institute and Department of Medical Biophysics and Immunology, University of Toronto, University Avenue, Toronto, Ontario M5G 2M9, Canada. |
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| 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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