title: β-myosin heavy chain is induced by pressure overload in a minor subpopulation of smaller mouse cardiac myocytes.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: VA Medical Center (111-C-8), 4150 Clement St, San Francisco, CA 94121, USA.
authors.forename: Javier E
authors.initials: JE
authors.lastname: López
authors.forename: Bat-Erdene
authors.initials: BE
authors.lastname: Myagmar
authors.forename: Philip M
authors.initials: PM
authors.lastname: Swigart
authors.forename: Megan D
authors.initials: MD
authors.lastname: Montgomery
authors.forename: Stephen
authors.initials: S
authors.lastname: Haynam
authors.forename: Marty
authors.initials: M
authors.lastname: Bigos
authors.forename: Manoj C
authors.initials: MC
authors.lastname: Rodrigo
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001018:Aortic Diseases / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry / Q000379:methods; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D024723:Ventricular Myosins / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology*
chemical_list: C551613:Myh7 protein, mouse; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains