Expression patterns of cardiac myofilament proteins

Jeanne L. Theis, J. Martijn Bos, Jason D. Theis, Dylan V. Miller, Joseph A. Dearani, Hartzell V. Schaff, Bernard J. Gersh, Steve R. Ommen, Richard L. Moss, Michael J. Ackerman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background-Mutations in myofilament proteins, most commonly MYBPC3-encoded myosin-binding protein C and MYH7-encoded ß-myosin heavy chain, can cause hypertrophic cardiomyopathy (HCM). Despite significant advances in structure-function relationships pertaining to the cardiac sarcomere, there is limited knowledge of how a mutation leads to clinical HCM. We, therefore, set out to study expression and localization of myofilament proteins in left ventricular tissue of patients with HCM. Methods and Results-Frozen surgical myectomy specimens from 47 patients with HCM were examined and genotyped for mutations involving 8 myofilament-encoding genes. Myofilament protein levels were quantified by Western blotting with localization graded from immunohistochemical staining of tissue sections. Overall, 25 of 47 (53%) patients had myofilament-HCM, including 12 with MYBPC3-HCM and 9 with MYH7-HCM. As compared with healthy heart tissue, levels of myofilament proteins were increased in patients manifesting a mutation in either gene. Patients with a frameshift mutation predicted to truncate MYBPC3 exhibited marked disturbances in protein localization as compared with missense mutations in either MYBPC3 or MYH7. Conclusions-In this first expression study in human HCM tissue, increased myofilament protein levels in patients with either MYBPC3-or MYH7-mediated HCM suggest a poison peptide mechanism. Specifically, the mechanism of dysfunction may vary according to the genetic subgroup suggested by a distinctly abnormal distribution of myofilament proteins in patients manifesting a truncation mutation in MYBPC3.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalCirculation: Heart Failure
Issue number4
StatePublished - Jul 2009


  • Cardiomyopathy
  • Genetics
  • Hypertrophy
  • Protein
  • Tissue

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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