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Journal of Molecular Medicine

, Volume 81, Issue 9, pp 566–577 | Cite as

Myocardin mRNA is augmented in the failing myocardium: expression profiling in the porcine model and human dilated cardiomyopathy

  • Mario Torrado
  • Eduardo López
  • Alberto Centeno
  • Constancio Medrano
  • Alfonso Castro-Beiras
  • Alexander T. MikhailovEmail author
Original Article

Abstract

The implication of myocardin and homeodomain only protein (HOP) in combinatorial molecular pathways that guide heart development and cardio-specific gene expression has recently been reported. However, expression of these genes in the failing heart has not yet been investigated. This study was designed to elaborate a molecular profile of myocardin and HOP expression in the failing ventricular myocardium through the use of both explanted human heart samples and heart biopsies from neonatal piglets with doxorubicin-induced cardiomyopathy (Dox-CM). Myocardin and HOP mRNA levels were estimated by both northern blot hybridization and semiquantitative RT-PCR in human ventricular preparations in end-stage failure due to dilated cardiomyopathy (DCM), as well as in nonfailing donor hearts. Similar experiments were performed with ventricular samples from normal and Dox-treated neonatal piglets. The gene expression of brain natriuretic peptide (BNP) was used as a molecular marker of myocardial damage and failure. The study revealed the following novel findings: (1) myocardin transcripts are detected in neonatal human and pig hearts at lower levels than in mature cardiac tissues, (2) the myocardin transcript pool is significantly augmented in the failing human and porcine myocardium as compared to that in nonfailing heart samples, (3) in the failing human myocardium, increased levels of myocardin mRNA are associated with a diminished HOP transcript content, and (4) the inverse proportion in cardiac myocardin/HOP mRNA pools observed in explanted human hearts is also traceable in normal human heart and aorta. A possible dual consequence of increased myocardin and decreased HOP expression levels on serum response factor-dependent cardiac-specific expression in the normal heart and at heart failure is discussed. Therefore, increased abundance of the myocardin mRNA pool is judged to be a novel CM-related feature which, alone or in association with decreased HOP transcript levels, can be responsible for dysregulation of myocardin-mediated gene expression in failing myocardium.

Keywords

Cardiomyopathy Gene expression Myocardin Heart failure 

Abbreviations

Dox-CM

Doxorubicin-induced cardiomyopathy

RT-PCR

Reverse transcriptase-polymerase chain reaction

BNP

Brain natriuretic peptide

ANP

Atrial natriuretic peptide

DCM

Dilated cardiomyopathy

LV

Left ventricle

RV

Right ventricle

LA

Left atrium

RA

Right atrium

AP

Apex of the heart

NIS

Normal isotonic saline

HOP

Homeodomain only protein

SRF

Serum response factor

SMC

Smooth muscle cells

UTR

Untranslated region

FW

Free-wall

MLC2v

Myosin light chain 2 ventricular form

SM-A

Smooth muscle alpha actin

Alpha-MHC

Alpha myosin heavy chain

Notes

Acknowledgements

This work was supported by a long-time grant (SAF2001-0910) from the Spanish Ministry of Science and Technology and by infrastructure funding (2002) from the Autonomic Government of Galicia (Spain). We thank Dr. Marisa Crespo and Dr. J. Muñiz for their help in sampling and characterization of human heart tissues. We are grateful to Dr. Esperanza Cerdán for welcoming our northern blot hybridization experiments in her laboratory. We wish to thank two anonymous reviewers for constructive comments on the first version of the manuscript.

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Mario Torrado
    • 1
  • Eduardo López
    • 2
  • Alberto Centeno
    • 2
  • Constancio Medrano
    • 2
  • Alfonso Castro-Beiras
    • 2
  • Alexander T. Mikhailov
    • 1
    Email author
  1. 1.Developmental Biology Unit, Institute of Health SciencesUniversity of La Coruña La CoruñaSpain
  2. 2.University Hospital "Juan Canalejo" La CoruñaSpain

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