Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger

Background: Cardiac hypertrophy is central to the etiology of heart failure. Understanding the molecular pathways promoting cardiac hypertrophy may identify new targets for therapeutic intervention. Sodium-proton exchanger (NHE1) activity and expression levels in the heart are elevated in many model...

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Autores principales: Sowah, D., Brown, B.F., Quon, A., Álvarez, Bernardo Víctor, Casey, J.R.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
Materias:
Ciencias Médicas
AE3
Bicarbonate transport
Cardiomyocyte hypertrophy
Chloride/bicarbonate exchange
Heart failure
pH regulation
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85641
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-85641
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
AE3
Bicarbonate transport
Cardiomyocyte hypertrophy
Chloride/bicarbonate exchange
Heart failure
pH regulation
spellingShingle Ciencias Médicas
AE3
Bicarbonate transport
Cardiomyocyte hypertrophy
Chloride/bicarbonate exchange
Heart failure
pH regulation
Sowah, D.
Brown, B.F.
Quon, A.
Álvarez, Bernardo Víctor
Casey, J.R.
Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger
topic_facet Ciencias Médicas
AE3
Bicarbonate transport
Cardiomyocyte hypertrophy
Chloride/bicarbonate exchange
Heart failure
pH regulation
description Background: Cardiac hypertrophy is central to the etiology of heart failure. Understanding the molecular pathways promoting cardiac hypertrophy may identify new targets for therapeutic intervention. Sodium-proton exchanger (NHE1) activity and expression levels in the heart are elevated in many models of hypertrophy through protein kinase C (PKC)/MAPK/ERK/p90RSK pathway stimulation. Sustained NHE1 activity, however, requires an acid-loading pathway. Evidence suggests that the Cl-/HCO3- exchanger, AE3, provides this acid load. Here we explored the role of AE3 in the hypertrophic growth cascade of cardiomyocytes.Methods: AE3-deficient (ae3-/-) mice were compared to wildtype (WT) littermates to examine the role of AE3 protein in the development of cardiomyocyte hypertrophy. Mouse hearts were assessed by echocardiography. As well, responses of cultured cardiomyocytes to hypertrophic stimuli were measured. pH regulation capacity of ae3-/- and WT cardiomyocytes was assessed in cultured cells loaded with the pH-sensitive dye, BCECF-AM.Results: ae3-/- mice were indistinguishable from wild type (WT) mice in terms of cardiovascular performance. Stimulation of ae3-/- cardiomyocytes with hypertrophic agonists did not increase cardiac growth or reactivate the fetal gene program. ae3-/- mice are thus protected from pro-hypertrophic stimulation. Steady state intracellular pH (pHi) in ae3-/- cardiomyocytes was not significantly different from WT, but the rate of recovery of pHi from imposed alkalosis was significantly slower in ae3-/- cardiomyocytes.Conclusions: These data reveal the importance of AE3-mediated Cl-/HCO3- exchange in cardiovascular pH regulation and the development of cardiomyocyte hypertrophy. Pharmacological antagonism of AE3 is an attractive approach in the treatment of cardiac hypertrophy.
format Articulo
Articulo
author Sowah, D.
Brown, B.F.
Quon, A.
Álvarez, Bernardo Víctor
Casey, J.R.
author_facet Sowah, D.
Brown, B.F.
Quon, A.
Álvarez, Bernardo Víctor
Casey, J.R.
author_sort Sowah, D.
title Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger
title_short Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger
title_full Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger
title_fullStr Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger
title_full_unstemmed Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger
title_sort resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the ae3 cl-/hco3- exchanger
publishDate 2014
url http://sedici.unlp.edu.ar/handle/10915/85641
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AT quona resistancetocardiomyocytehypertrophyinae3micedeficientintheae3clhco3exchanger
AT alvarezbernardovictor resistancetocardiomyocytehypertrophyinae3micedeficientintheae3clhco3exchanger
AT caseyjr resistancetocardiomyocytehypertrophyinae3micedeficientintheae3clhco3exchanger
bdutipo_str Repositorios
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