Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart

Background: Carbonic anhydrase enzymes (CA) catalyze the reversible hydration of carbon dioxide to bicarbonate in mammalian cells. Trans-membrane transport of CA-produced bicarbonate contributes significantly to cellular pH regulation. A body of evidence implicates pH-regulatory processes in the hyp...

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Autores principales: Álvarez, Bernardo Víctor, Quon, Anita L., Mullen, John, Casey, Joseph R.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2013
Materias:
Ciencias Médicas
Carbonic anhydrase
Cardiac hypertrophy
Gene expression
Heart failure
Heart transplant
pH regulation
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85089
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-85089
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
Carbonic anhydrase
Cardiac hypertrophy
Gene expression
Heart failure
Heart transplant
pH regulation
spellingShingle Ciencias Médicas
Carbonic anhydrase
Cardiac hypertrophy
Gene expression
Heart failure
Heart transplant
pH regulation
Álvarez, Bernardo Víctor
Quon, Anita L.
Mullen, John
Casey, Joseph R.
Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
topic_facet Ciencias Médicas
Carbonic anhydrase
Cardiac hypertrophy
Gene expression
Heart failure
Heart transplant
pH regulation
description Background: Carbonic anhydrase enzymes (CA) catalyze the reversible hydration of carbon dioxide to bicarbonate in mammalian cells. Trans-membrane transport of CA-produced bicarbonate contributes significantly to cellular pH regulation. A body of evidence implicates pH-regulatory processes in the hypertrophic growth pathway characteristic of hearts as they fail. In particular, Na+/H+ exchange (NHE) activation is pro-hypertrophic and CA activity activates NHE. Recently Cardrase (6-ethoxyzolamide), a CA inhibitor, was found to prevent and revert agonist-stimulated cardiac hypertrophy (CH) in cultured cardiomyocytes. Our goal thus was to determine whether hypertrophied human hearts have altered expression of CA isoforms.Methods: We measured CA expression in hypertrophied human hearts to begin to examine the role of carbonic anhydrase in progression of human heart failure. Ventricular biopsies were obtained from patients undergoing cardiac surgery (CS, n = 14), or heart transplantation (HT, n = 13). CS patients presented mild/moderate concentric left ventricular hypertrophy and normal right ventricles, with preserved ventricular function; ejection fractions were ~60%. Conversely, HT patients with failing hearts presented CH or ventricular dilation accompanied by ventricular dysfunction and EF values of 20%. Non-hypertrophic, non-dilated ventricular samples served as controls.Results: Expression of atrial and brain natriuretic peptide (ANP and BNP) were markers of CH. Hypertrophic ventricles presented increased expression of CAII, CAIV, ANP, and BNP, mRNA levels, which increased in failing hearts, measured by quantitative real-time PCR. CAII, CAIV, and ANP protein expression also increased approximately two-fold in hypertrophic/dilated ventricles.Conclusions: These results, combined with in vitro data that CA inhibition prevents and reverts CH, suggest that increased carbonic anhydrase expression is a prognostic molecular marker of cardiac hypertrophy.
format Articulo
Articulo
author Álvarez, Bernardo Víctor
Quon, Anita L.
Mullen, John
Casey, Joseph R.
author_facet Álvarez, Bernardo Víctor
Quon, Anita L.
Mullen, John
Casey, Joseph R.
author_sort Álvarez, Bernardo Víctor
title Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
title_short Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
title_full Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
title_fullStr Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
title_full_unstemmed Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
title_sort quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
publishDate 2013
url http://sedici.unlp.edu.ar/handle/10915/85089
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AT quonanital quantificationofcarbonicanhydrasegeneexpressioninventricleofhypertrophicandfailinghumanheart
AT mullenjohn quantificationofcarbonicanhydrasegeneexpressioninventricleofhypertrophicandfailinghumanheart
AT caseyjosephr quantificationofcarbonicanhydrasegeneexpressioninventricleofhypertrophicandfailinghumanheart
bdutipo_str Repositorios
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