Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor-Mediated Cardiomyocyte Autophagy

Porrello, Enzo R., D'Amore, Angelo, Curl, Claire L., Allen, Andrew M., Harrap, Stephen B., Thomas, Walter G. and Delbridge, Lea M. D. (2009) Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor-Mediated Cardiomyocyte Autophagy. Hypertension, 53 6: 1032-1040. doi:10.1161/HYPERTENSIONAHA.108.128488


Author Porrello, Enzo R.
D'Amore, Angelo
Curl, Claire L.
Allen, Andrew M.
Harrap, Stephen B.
Thomas, Walter G.
Delbridge, Lea M. D.
Title Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor-Mediated Cardiomyocyte Autophagy
Journal name Hypertension   Check publisher's open access policy
ISSN 0194-911X
Publication date 2009
Year available 2009
Sub-type Article (original research)
DOI 10.1161/HYPERTENSIONAHA.108.128488
Volume 53
Issue 6
Start page 1032
End page 1040
Total pages 9
Place of publication United State
Publisher Lippincott Williams & Wilkins
Collection year 2010
Language eng
Subject C1
060110 Receptors and Membrane Biology
920103 Cardiovascular System and Diseases
Abstract Autophagy has emerged as an important process in the pathogenesis of cardiovascular diseases, but the proximal triggers for autophagy are unknown. Angiotensin II plays a central role in the pathogenesis of cardiac hypertrophy and heart failure. In this study, we used angiotensin II type 1 (AT1) and type 2 (AT2) receptor–expressing adenoviruses in cultured neonatal cardiomyocytes to provide the first demonstration that neonatal cardiomyocyte autophagic activity is differentially modulated by AT1 and AT2 receptor subtypes. Angiotensin II stimulation (48 hours) of neonatal cardiomyocytes expressing the AT1 receptor alone (Ad-AT1; 10 multiplicities of infection) induced a significant increase in the number of HcRed-LC3 autophagosomes per cell (17.3±1.6 versus 33.3±4.1 autophagosomes per cell; P<0.05). Coexpression of a high ratio of AT2:AT1 (Ad-AT2:Ad-AT1 multiplicity of infection ratio: 20:5) receptors completely abrogated the AT1-mediated increase in autophagy (9.3±1.4 versus 33.3±4.1 autophagosomes per cell; P<0.05). Treatment with the AT2 receptor antagonist PD123319 did not reverse the AT2-mediated antiautophagic effect. AT1- and AT2-mediated autophagic responses were also assessed in cardiomyocytes from a genetic model that exhibits neonatal myocardial growth suppression. In these neonate myocyte cultures, AT1 receptor activation induced a marked increase in the number of myocytes containing cytoplasmic vacuoles compared with the control (22.7±4.1% versus 1.1±0.6%; P<0.001) and was characterized by a nonapoptotic autophagic phenotype. The incidence of cardiomyocyte autophagic vacuolization in this myocyte population decreased dramatically to only 0.4±0.2% in myocytes infected with a high ratio of Ad-AT2:Ad-AT1. This study provides the first description of reciprocal regulation of cardiomyocyte autophagic induction by the AT1 and AT2 receptor subtypes.
Keyword angiotensin II
angiotensin II type 1 receptor
angiotensin II type 2 receptor
autophagy
hypertrophic heart rat
hypertrophy
neonate
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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Created: Tue, 07 Jul 2009, 09:19:34 EST by Shirley Rey on behalf of School of Biomedical Sciences