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Calreticulin induces dilated cardiomyopathy

Dukgyu Lee1, Tatsujiro Oka, Beth Hunter

  • 1Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.

Plos One
|February 26, 2013
PubMed

Insights

Upregulating calreticulin in adult hearts impairs cardiac function, leading to heart failure. This study reveals calreticulin

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Endoplasmic Reticulum Biology

Background:

  • Calreticulin is crucial for embryonic heart development but downregulated in adult hearts.
  • Adult hearts normally have minimal calreticulin levels.
  • The role of calreticulin in the adult heart remained largely unexplored.

Purpose of the Study:

  • To investigate the functional role of calreticulin in the adult mammalian heart.
  • To determine the consequences of calreticulin re-expression in adult cardiac tissue.

Main Methods:

  • Generation of an inducible transgenic mouse model with cardiac-specific calreticulin upregulation via Cre/loxP system.
  • Echocardiography to assess cardiac function (systolic, diastolic, valve function).
  • Analysis of gene and protein expression related to calcium signaling and cardiac structure.

Main Results:

  • Calreticulin upregulation in adult hearts led to impaired left ventricular systolic and diastolic function.
  • Mitral valve function was also compromised in transgenic mice.
  • Downregulation of key calcium-handling proteins and altered expression of gap junction proteins were observed.

Conclusions:

  • Overexpression of calreticulin in adult hearts induces cardiomyopathy and heart failure in vivo.
  • Cardiac dysfunction is linked to altered calcium handling, gap junction alterations, and left ventricle remodeling.
  • Calreticulin re-expression significantly disrupts adult cardiac homeostasis.
Abstract

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