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Open Access Highly Accessed Research article

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

Bernardo V Alvarez1, Anita L Quon2, John Mullen3 and Joseph R Casey2*

Author Affiliations

1 Universidad Nacional de La Plata, La Plata, Argentina

2 Department of Biochemistry, and Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB, T6G 2H7, Canada

3 Department of Surgery, University of Alberta, Edmonton, AB, T6G 2H7, Canada

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BMC Cardiovascular Disorders 2013, 13:2  doi:10.1186/1471-2261-13-2

Published: 8 January 2013

Abstract

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, nā€‰=ā€‰14), or heart transplantation (HT, nā€‰=ā€‰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.

Keywords:
Heart failure; Carbonic anhydrase; pH regulation; Gene expression; Heart transplant; Cardiac hypertrophy