Abstract
Background: Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in genes encoding sarcomeric proteins. Previously, we observed a reduced maximal force generating capacity (Fmax) of cardiomyocytes from HCM patients with mutations in myosin-binding protein-C (MYBPC3). In this study we investigated the contribution of myofibril density (MyoD) and cross-sectional area (CSA) to the reduction in Fmax.Methods: We measured Fmax and CSA of single permeabilized ventricular cardiomyocytes of 27 HCM patients with mutations in MYBPC3, myosin heavy chain: MYH7, troponin T: TNNT2 and troponin I: TNNI3 and 10 non-failing donor hearts. MyoD was calculated as the sum of myofibril area related to cell area assessed by electron microscopy.Results: Average Fmax was significantly lower in HCM groups compared to donor (Figure A). Figure B shows that MyoD of HCM hearts was reduced compared to donors. CSA of HCM hearts (529±48μm2) was significantly higher compared to donors (342±12μm2). Linear regression analysis revealed a significant negative linear relationship between CSA and Fmax (R2= 0.50, β=-0.023, p=0.014).Conclusion: Cardiomyocyte hypertrophy and reduced myofibrillar density underlie depressed Fmax in HCM with mutations in thick and thin sarcomeric proteins.View Large Image | View Hi-Res Image | Download PowerPoint Slide
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