Key result
Decreased isoproterenol-induced cell shortening following transverse aortic constriction occurs only in hypertrophic cardiomyocytes that re-express beta-myosin heavy chain.
Why the study?
Does the reduction in beta-adrenergic responsiveness in cardiac hypertrophy occur concordantly with beta-MHC re-expression in individual cardiomyocytes?
Does the reduction in beta-adrenergic responsiveness in cardiac hypertrophy occur concordantly with beta-MHC re-expression in individual cardiomyocytes?
In cardiac hypertrophy, the pathological reduction in beta-adrenergic responsiveness is restricted to the specific subset of cardiomyocytes that re-express the fetal gene beta-MHC.
Animal myocyte data on hypertrophy markers warrant clinical caution; leaves open whether beta-MHC and beta-adrenergic changes are cell-concordant in humans.
AIMS: Cardiac hypertrophy is associated with a reduction in the contractile response to beta-adrenergic stimulation, and with re-expression of foetal genes such as beta-myosin heavy chain (MHC). However, whether these two markers of pathology develop concordantly in the same individual cells or independently in different cells is not known. METHODS AND RESULTS: To answer this question, we examined the beta-adrenergic response of individual beta-MHC expressing and non-expressing myocytes from hypertrophic hearts, using a previously generated mouse model (YFP/beta-MHC) in which a yellow fluorescent protein (YFP) is fused to the native beta-MHC protein allowing easy identification of beta-MHC expressing cells. Yellow fluorescent protein/beta-MHC mice were submitted to 4 weeks of transverse aortic constriction (TAC), and the contractile parameters of isolated individual myocytes in response to the beta-adrenergic agonist isoproterenol were assessed. Our results demonstrate that the decrease in isoproterenol-induced cell shortening that develops in TAC hearts occurs only in those hypertrophic myocytes that re-express beta-MHC. Hypertrophic myocytes that do not express beta-MHC have contractility indices indistinguishable from non-TAC controls. CONCLUSION: These data show that the reduction of beta-adrenergic response occurs only in subsets, rather than in all myocytes, and is coincident with re-expression of beta-MHC.
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Pandya et al. (2009) studied Cardiac hypertrophy. beta-MHC re-expression vs. Hypertrophic myocytes not expressing beta-MHC and non-TAC controls was evaluated on Isoproterenol-induced cell shortening. Decreased isoproterenol-induced cell shortening following transverse aortic constriction occurs only in hypertrophic cardiomyocytes that re-express beta-myosin heavy chain.
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