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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/H1274    most recent 00174.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yan, X. Articles by Morgan, J. P. Search for Related Content PubMed PubMed Citation Articles by Yan, X. Articles by Morgan, J. P.

Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT₂ receptors in ventricular myocytes

¹Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine and ²Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; and ³Department of Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina

Submitted 17 February 2006 ; accepted in final form 14 December 2007

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.

cardiomyocyte; angiotensin II type 2 receptor; gene expression; protein expression