Leukemia inhibitory factor is augmented in the heart in experimental heart failure

Michihisa Jougasaki, Hanna Leskinen, Amy M. Larsen, Alessandro Cataliotti, Horng H. Chen, John C. Burnett

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that induces cardiac myocyte hypertrophy through the signal transducing molecule, glycoprotein 130. To date, localization of LIF in the heart and regulation of cardiac LIF expression in congestive heart failure (CHF) remain undefined. The present study investigates the potential activation of LIF expression in the failing canine heart that was produced by progressive rapid ventricular pacing. Immunohistochemistry for LIF revealed that LIF immunoreactivity was present in the atrial and ventricular myocytes of the normal heart and was markedly increased in the failing heart as compared to the normal heart. Northern blot analysis demonstrated that cardiac LIF mRNA was increased in both atrium and ventricle in CHF as compared to the normal heart (P < 0.01). Linear regression analysis revealed a positive correlation between atrial LIF mRNA and atrial pressure (r = 0.87, P < 0.001 in right atrium and r = 0.86, P < 0.001 in left atrium). Positive correlations between left ventricular LIF mRNA and left ventricular dimensions (r = 0.91, P < 0.0001 in end-systolic diameter; r = 0.86, P < 0.001 in end-diastolic diameter), and an inverse correlation between left ventricular LIF mRNA and left ventricular ejection fraction (EF) were observed (r = -0.93, P < 0.0001). There was a positive correlation between left ventricular LIF mRNA and left ventricular mass index (LVMI) (r = 0.85, P < 0.001). The present study demonstrates that cardiac LIF immunoreactivity and its gene expression are increased in a canine model of experimental CHF and suggests a potential role for LIF in the pathophysiology of CHF.

Original languageEnglish (US)
Pages (from-to)137-145
Number of pages9
JournalEuropean Journal of Heart Failure
Volume5
Issue number2
DOIs
StatePublished - Mar 1 2003

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Keywords

  • Congestive
  • Cytokines
  • Gene expression
  • Heart failure
  • Immunohistochemistry
  • Northern blot analysis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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