Changes in titin and collagen underlie diastolic stiffness diversity of cardiac muscle

Yiming Wu, Olivier Cazorla, Dietmar Labeit, Siegfried Labeit, Henk Granzier

Research output: Contribution to journalArticlepeer-review

173 Scopus citations


Small (N2B) and large (N2BA) cardiac titin isoforms are differentially expressed in a species-specific and heart location-specific manner. To understand how differential expression of titin isoforms may influence passive stiffness of cardiac muscle we investigated the mechanical properties of mouse left ventricular (MLV) wail muscle (expressing predominantly the small titin isoform), bovine left atrial (BLA) wall muscle (predominantly the large isoform), and bovine left ventricnlar (BLV) wall muscle (expressing small and large isoforms at similar levels). Results indicate that the overall passive muscle stiffness of the muscle types varies nearly ten-fold with stiffness increasing in the following order: BLA, BLV and MLV. To investigate the basis of the variation in the overall muscle stiffness, the contributions of titin and collagen to muscle stiffness were determined. Results showed that increased muscle stiffness results from increases in both titin- and collagen-based passive stiffness, indicating that titin and collagen change in a coordinated fashion. The expression level of the small titin isoform correlates with titin's contribution to overall muscle stiffness, suggesting that differential expression of titin isoforms is an effective means to modulate the filling behavior of the heart.

Original languageEnglish (US)
Pages (from-to)2151-2161
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Issue number12
StatePublished - 2000


  • Connectin
  • Diastole
  • Elasticity
  • Muscle mechanics
  • Passive force

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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