Molecular basis of ventricular arrhythmogenicity in a Pgc-1α deficient murine model

Figures

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  Fig. 1. Stratifications of individual genes by fold changes and significance level in the comparison of Pgc-1α−/− and WT ventricles. Volcano plot summarizing the effects of Pgc-1α−/− genotype on ventricular gene transcription. Magnitude of change in transcription levels as expressed as log2 transformed fold changes plotted against the level of statistical significance as the unadjusted P-values from independent Student's t-tests.

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  Fig. 2. (A) NaV1.5 expression levels in WT (N = 4) and Pgc-1α−/− (N = 4) ventricles obtained by densitometric analysis and their representative Western blots including the housekeeping protein. (B) Cx43 expression levels in WT (N = 4) and Pgc-1α−/− (N = 4) ventricles obtained by densitometric analysis and their representative Western blots including the housekeeping protein. Initial bicinchoninic acid (BCA) assay estimate of lysate protein concentration determined lysate volumes ensuring equal amounts of protein in each well. Measurements made along with a further control housekeeping protein (β -tubulin (A), β-actin (B)) not affected by the difference in genotype, for normalization of the protein of interest to control for any residual variation in amount of protein loaded in each well.

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  Fig. 3. (A) Shows percentage fibrotic tissue in WT (N = 8) and Pgc-1α−/− (N = 9) ventricles obtained by histological analysis. (B) Shows representative example of the absence of fibrotic change in old WT ventricles (i) and the presence of fibrotic change in old Pgc-1α−/− ventricles obtained by histological analysis (length of scale bar: 250 μm).

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  Fig. 4. Molecules implicated in electrophysiological changes with mitochondrial dysfunction. Solid lines: changes suggested in the present experiments. Dotted lines: other relevant changes discussed in the paper reported in other experiments. Arrow-end: positive effects increasing activity/expression; straight horizontal-end: negative effects decreasing activity/ expression. Created using BioRender.com.