?-myosin heavy chain is induced by pressure overload in a minor subpopulation of smaller mouse cardiac myocytes.

ABSTRACT: Induction of the fetal hypertrophic marker gene ?-myosin heavy chain (?-MyHC) is a signature feature of pressure overload hypertrophy in rodents. ?-MyHC is assumed present in all or most enlarged myocytes.To quantify the number and size of myocytes expressing endogenous ?-MyHC by a flow cytometry approach.Myocytes were isolated from the left ventricle of male C57BL/6J mice after transverse aortic constriction (TAC), and the fraction of cells expressing endogenous ?-MyHC was quantified by flow cytometry on 10,000 to 20,000 myocytes with use of a validated ?-MyHC antibody. Side scatter by flow cytometry in the same cells was validated as an index of myocyte size. ?-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). ?-MyHC-positive myocytes did not enlarge with TAC and were smaller at all times than myocytes without ?-MyHC (?70% as large, P<0.001). ?-MyHC-positive myocytes arose by addition of ?-MyHC to ?-MyHC and had more total MyHC after TAC than did the hypertrophied myocytes that had ?-MyHC only. Myocytes positive for ?-MyHC were found in discrete regions of the left ventricle in 3 patterns: perivascular, in areas with fibrosis, and in apparently normal myocardium.?-MyHC protein is induced by pressure overload in a minor subpopulation of smaller cardiac myocytes. The hypertrophied myocytes after TAC have ?-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.

SUBMITTER: Lopez JE 

PROVIDER: S-EPMC3166391 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature