[摘要]：Rationale: Induction of the fetal hypertrophic marker gene beta-myosin heavy chain (beta-MyHC) is a signature feature of pressure overload hypertrophy in rodents. beta-MyHC is assumed present in all or most enlarged myocytes. Objective: To quantify the number and size of myocytes expressing endogenous beta-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 beta-MyHC was quantified by flow cytometry on 10 000 to 20 000 myocytes with use of a validated beta-MyHC antibody. Side scatter by flow cytometry in the same cells was validated as an index of myocyte size. beta-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). beta-MyHC-positive myocytes did not enlarge with TAC and were smaller at all times than myocytes without beta-MyHC (approximate to 70% as large, P<0.001). beta-MyHC-positive myocytes arose by addition of beta-MyHC to alpha-MyHC and had more total MyHC after TAC than did the hypertrophied myocytes that had alpha-MyHC only. Myocytes positive for beta-MyHC were found in discrete regions of the left ventricle in 3 patterns: perivascular, in areas with fibrosis, and in apparently normal myocardium. Conclusions: beta-MyHC protein is induced by pressure overload in a minor subpopulation of smaller cardiac myocytes. The hypertrophied myocytes after TAC have alpha-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. (Circ Res. 2011;109:629-638.)
