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PMID:12075344
| Citation |
Crackower, MA, Sarao, R, Oudit, GY, Yagil, C, Kozieradzki, I, Scanga, SE, Oliveira-dos-Santos, AJ, da Costa, J, Zhang, L, Pei, Y, Scholey, J, Ferrario, CM, Manoukian, AS, Chappell, MC, Backx, PH, Yagil, Y and Penninger, JM (2002) Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417:822-8 |
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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. |
| Links |
PubMed Online version:10.1038/nature00786 |
| Keywords |
Angiotensin II/blood; Angiotensin II/metabolism; Animals; Anoxia/genetics; Blood Pressure/genetics; Cloning, Molecular; Drosophila Proteins; Drosophila melanogaster/enzymology; Drosophila melanogaster/genetics; Drosophila melanogaster/physiology; Female; Gene Deletion; Gene Expression Regulation, Enzymologic; Heart/physiology; Heart/physiopathology; Hypertension/genetics; Male; Metalloendopeptidases/deficiency; Metalloendopeptidases/genetics; Metalloendopeptidases/metabolism; Mice; Mice, Knockout; Myocardial Contraction; Myocardium/enzymology; Peptidyl-Dipeptidase A/deficiency; Peptidyl-Dipeptidase A/genetics; Peptidyl-Dipeptidase A/metabolism; Quantitative Trait, Heritable; Radiation Hybrid Mapping; Rats; Up-Regulation; X Chromosome/genetics |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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References
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