BRG1 is a biomarker of hypertrophic cardiomyopathy in human heart specimens

Figures

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  Figure 1. Fetal cardiac tissue expresses BRG1 prior to 24 weeks’ gestation. (a) SMARCA4/BRG1 expression visualized at 18 weeks and 24 weeks. Top panel shows H&E stained sample, bottom panel shows high power BRG1 immunohistochemistry. Scale bar represents 100 µm. (b) BRG1 expression is significantly elevated in fetal heart tissue in the first 17–24 weeks of development. Fetal cardiac tissue beyond 25 weeks’ gestations shows no significant difference in BRG1 expression relative to healthy adult controls. Data show proportions of subjects that fell into each BRG1 expression tier. ** denotes p < 0.01. Graph generated with GraphPad Prism 9.1.1 (GraphPad, San Diego, CA) by JCS.

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  Figure 2. Adult cardiomyocytes express elevated protein levels of BRG1/SMARCA4 in hypertrophic cardiomyopathy. (a) BRG1/SMARCA4 protein expression visualized in healthy adult cardiomyocytes (left) and adult cardiomyocytes with HCM (right). Top panel shows H&E stained sample, bottom panel shows high power BRG1/SMARCA4 immunohistochemistry. Scale bars represent 50 µm. (b) HCM tissue in discovery cohort show increased BRG1/SMARCA4 protein expression relative to healthy controls. Data presented as mean + SEM. **** denotes p < 0.0001. (c) HCM tissue in validation cohort show increased BRG1/SMARCA4 protein expression relative to healthy controls. Data show proportions of subjects that fell into each BRG1/SMARCA4 protein expression tier. (d) HCM tissue in validation cohort do not show a significant difference in BRM/SMARCA2 protein expression compared to controls. However, DCM hearts show reduced BRM/SMARCA2 protein expression relative to healthy controls, IHD and SCD hearts. Data presented as mean + SEM. *** denotes p < 0.001, ** denotes p < 0.01. Graphs generated with GraphPad Prism 9.1.1 (GraphPad, San Diego, CA) by JCS.

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  Figure 3. BRG1 inhibition reduces gene expression of MYH7 without altering cardiac troponin. (a) Quantification of TNNI1, TNNI3, MYH6, MYH7, and BRG1 expression during the first 2 weeks following cardiac differentiation from human iPSCs demonstrates increased MYH7 and TNNI3, as well as elevated BRG1. (b) Inhibition of BRG1 significantly reduces MYH7 (p < 0.05). Data presented as log2 fold change ± SEM. Graph generated with GraphPad Prism 9.1.1 (GraphPad, San Diego, CA) by JCS.