Micro-biopsy for detection of gene expression changes in ischemic swine myocardium: A pilot study

Figures

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  Fig 1. Experimental design. (A) Baseline micro-EMB was followed by a 60 minutes occlusion of distal left anterior descending artery. Repeated micro-EMB was performed before, during, and after occlusion at 1–3 hours, two days and 14 days. (B) Post-mortem image of the resulting necrotic area in the right peri-apical wall (approximately 5 x 11 mm). (C) Fluoroscopy in posteroanterior view, showing sampling from apical (infarcted) and lateral (non-infarcted) regions (arrows). Panel A contains elements reproduced from Springer Nature [5] under Creative Commons License CC-BY 4.0.

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  Fig 2. Differential expression analysis. (A) Chord plot of top regulated genes and corresponding enriched biological processes from differential expression analysis between infarcted samples (n = 24). (B) Heatmap of top regulated genes (n = 1000) with hierarchical clustering showing two main groups, where the right cluster is exclusively composed by samples from the first hours after the occlusion. Values are normalized expression values centered and scaled in the row direction. (C) Heatmap of the same genes as in B, but also including samples from the non-infarction region (n = 18). Two samples from non-infarction region (arrows) are clustered with infarcted 1–3 hour samples.

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  Fig 3. Longitudinal plots of average gene expression values (normalized and transformed counts) for top regulated genes from each timepoint compared to baseline. (A) Top genes (n = 5) for the 0–1 hours timepoint. (B) Top genes (n = 5) for the 1–3 hours timepoint. (C) Top genes (n = 5) for the two days timepoint. Novel gene1 = ENSSSCG00000014997.

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  Fig 4. Estimated proportions of cell types in myocardial samples (n = 12). (A) Estimated proportion of fibroblasts. Significant difference between baseline and day two samples (unpaired t-test, adjusted p value < 0.02), as well as between day two and day 14 samples (adjusted p value < 0.02). (B). Estimated macrophage proportion. No significant differences between groups (adjusted p values > 0.05). (C) Estimated proportion of cardiomyocytes. Significant difference between baseline and day two samples (adjusted p value < 0.01), as well as between day two and day 14 samples (adjusted p value < 0.01). (D) Estimated endothelial cell proportion. No significant differences between groups (adjusted p values > 0.05).