title: 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.
authors.affiliation: Amgen Research Institute/Ontario Cancer Institute and Department of Medical Biophysics and Immunology, University of Toronto, University Avenue, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Crackower
authors.forename: Renu
authors.initials: R
authors.lastname: Sarao
authors.forename: Gavin Y
authors.initials: GY
authors.lastname: Oudit
authors.forename: Chana
authors.initials: C
authors.lastname: Yagil
authors.forename: Ivona
authors.initials: I
authors.lastname: Kozieradzki
authors.forename: Sam E
authors.initials: SE
authors.lastname: Scanga
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Oliveira-dos-Santos
authors.forename: Joan
authors.initials: J
authors.lastname: da Costa
authors.forename: Liyong
authors.initials: L
authors.lastname: Zhang
authors.forename: York
authors.initials: Y
authors.lastname: Pei
authors.forename: James
authors.initials: J
authors.lastname: Scholey
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.forename: Armen S
authors.initials: AS
authors.lastname: Manoukian
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.forename: Peter H
authors.initials: PH
authors.lastname: Backx
authors.forename: Yoram
authors.initials: Y
authors.lastname: Yagil
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics; D000860:Hypoxia / Q000235:genetics; D008297:Male; D008666:Metalloendopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019655:Quantitative Trait, Heritable; D021101:Radiation Hybrid Mapping; D051381:Rats; D015854:Up-Regulation; D014960:X Chromosome / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D000804:Angiotensin II; C102762:Acer protein, Drosophila; D007703:Peptidyl-Dipeptidase A; D008666:Metalloendopeptidases