title: Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes.
abstract: The role of the angiotensin II type 2 (AT2) receptor in cardiac hypertrophy remains controversial. We studied the effects of AT2 receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing AT2 (AT2TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in AT2TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between AT2TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in AT2TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between AT2TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in AT2TG-AS than in NTG-AS mice. iNOS was higher in AT2TG-AS than in NTG-AS mice but not significantly different. Our results indicate that AT2 receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice.
authors.affiliation: Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Brighton, MA 02135, USA.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yan
authors.forename: Adam J T
authors.initials: AJ
authors.lastname: Schuldt
authors.forename: Robert L
authors.initials: RL
authors.lastname: Price
authors.forename: Ivo
authors.initials: I
authors.lastname: Amende
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Liu
authors.forename: Katashi
authors.initials: K
authors.lastname: Okoshi
authors.forename: Kalon K L
authors.initials: KK
authors.lastname: Ho
authors.forename: Adèle J
authors.initials: AJ
authors.lastname: Pope
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Borg
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Lorell
authors.forename: James P
authors.initials: JP
authors.lastname: Morgan
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D006332:Cardiomegaly / Q000235:genetics* / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics* / Q000502:physiology; D016019:Survival Analysis; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D003094:Collagen