β-Myosin heavy chain is induced by pressure overload in a minor subpopulation of smaller mouse cardiac myocytes

Javier E Lopez, Bat Erdene Myagmar, Philip M. Swigart, Megan D. Montgomery, Stephen Haynam, Marty Bigos, Manoj C. Rodrigo, Paul C. Simpson

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

RATIONALE: Induction of the fetal hypertrophic marker gene β-myosin heavy chain (β-MyHC) is a signature feature of pressure overload hypertrophy in rodents. β-MyHC is assumed present in all or most enlarged myocytes. OBJECTIVE: To quantify the number and size of myocytes expressing endogenous β-MyHC by a flow cytometry approach. METHODS AND RESULTS: Myocytes were isolated from the left ventricle of male C57BL/6J mice after transverse aortic constriction (TAC), and the fraction of cells expressing endogenous β-MyHC was quantified by flow cytometry on 10 000 to 20 000 myocytes with use of a validated β-MyHC antibody. Side scatter by flow cytometry in the same cells was validated as an index of myocyte size. β-MyHC-positive myocytes constituted 3±1% of myocytes in control hearts (n=12), increasing to 25±10% at 3 days to 6 weeks after TAC (n=24, P<0.01). β-MyHC-positive myocytes did not enlarge with TAC and were smaller at all times than myocytes without β-MyHC (≈70% as large, P<0.001). β-MyHC-positive myocytes arose by addition of β-MyHC to α-MyHC and had more total MyHC after TAC than did the hypertrophied myocytes that had α-MyHC only. Myocytes positive for β-MyHC were found in discrete regions of the left ventricle in 3 patterns: perivascular, in areas with fibrosis, and in apparently normal myocardium. CONCLUSIONS: β-MyHC protein is induced by pressure overload in a minor subpopulation of smaller cardiac myocytes. The hypertrophied myocytes after TAC have α-MyHC only. These data challenge the current paradigm of the fetal hypertrophic gene program and identify a new subpopulation of smaller working ventricular myocytes with more myosin.

Original languageEnglish (US)
Pages (from-to)629-638
Number of pages10
JournalCirculation Research
Volume109
Issue number6
DOIs
StatePublished - Sep 2 2011

Keywords

  • β-myosin heavy chain
  • cardiac hypertrophy
  • cardiac monocytes
  • fetal genes
  • flow cytometry
  • pressure overload

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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