title: ACE2 deficiency induced perivascular fibrosis and cardiac hypertrophy during postnatal development in mice.
abstract: In order to investigate the role of angiotensin-converting enzyme 2 (ACE2) in cardiac development, we examined the effects of ACE2 deficiency on postnatal development of the heart using ACE2-knockout (ACE2KO) mice. Heart samples of wild type (WT; C57BL/6J) mice and ACE2KO mice were taken at 1, 4, and 10 weeks of age. In WT mice, expression of ACE2 mRNA increased from 1 week to 10 weeks. A similar increase was observed in immunostaining of ACE2 in the heart, in which ACE2 was strongly expressed in coronary arteries. Compared with WT mice, heart weight was greater in ACE2KO mice at 4 weeks, and coronary artery thickening and perivascular fibrosis were also already enhanced from 4 weeks. Consistent with the increase of fibrosis, cardiac expression of collagen and TIMP was higher, and expression of MMP was lower in ACE2KO mice at 4 weeks. In addition, TGF-β mRNA was also higher, and lower expression of PPARγ mRNA was observed at 4 weeks in ACE2KO mice. These results suggest that ACE2 plays an important role in postnatal development of the heart, and that lack of ACE2 enhances coronary artery remodeling with an increase in perivascular fibrosis and cardiac hypertrophy already around the weaning period.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Tohon, Japan.
authors.forename: Tomozo
authors.initials: T
authors.lastname: Moritani
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Harumi
authors.initials: H
authors.lastname: Kanno
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Nakaoka
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.forename: Takashi
authors.initials: T
authors.lastname: Higaki
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D000367:Age Factors; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006321:Heart / Q000254:growth & development* / Q000502:physiology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: ACE2; cardiac hypertrophy; development; fibrosis