The molecular signature of degeneration in explanted decellularized allogeneic heart valves

Figures

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  Figure 1. Overview of differentially expressed genes. (A) Venn diagram showing differentially expressed genes in decellularized explanted aortic valves (Homografts AV) and pulmonary valves (Homografts PV) compared with respective control heart valves. Increased and decreased expression of genes is indicated by arrowheads. (B,C) Principal component analysis (PCA) of the inflammation and fibrosis panel gene sets showing clusters of explanted decellularized pulmonary (PK) and aortic (AK) homografts as well as control heart valves. Each dot stands for one valve.

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  Figure 2. Explanted decellularized aortic valve homografts vs. controls. (A) Venn Diagram summarizing differentially regulated genes of explanted decellularized aortic valves compared with control aortic valves classified into functional categories. Increased/decreased transcript levels are indicated by arrowheads. (B,C) Principal component analysis (PCA) of the fibrosis and inflammation panel showing clusters of explanted decellularized aortic homografts (AK) and control aortic valves (AK_K). Each dot stands for one valve. (D) Volcano plot portraying the top differentially expressed genes of explanted decellularized aortic homografts vs. control aortic valves.

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  Figure 3. Explanted decellularized pulmonary valve homografts vs. controls. (A) Venn Diagram summarizing differentially regulated genes of decellularized explanted pulmonary valves compared with control pulmonary valves classified into functional categories. Up- and down-regulation of genes are indicated by arrowheads. (B,C) Principal component analysis (PCA) of the fibrosis and inflammation panel showing clusters of explanted decellularized pulmonary homografts (PK) and control pulmonary valves (PK_control). Each dot stands for one valve. (C) Volcano plot portraying differentially expressed genes of explanted decellularized pulmonary homografts vs. control pulmonary valves.

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  Figure 4. Protein expression analysis. (A) Elastica-van-Giesson (EvG) staining of a representative control heart valve (A, framed area magnified in B) and a degenerated homograft (C, framed area magnified in D). Arrows are highlighting the heart valve. (B) Immunohistochemical stainings of endothelial markers (PECAM1, CDH5), the chemokine CXCL12, the hypoxia marker HIF-1α, and the extracellular matrix protein COL3. Arrows are highlighting small vessels in E, G, I, and M and the endothelial lining in F. Scale bars equal 40 µm in A, J, and L, 20 µm in C, 100 µm in B, D, G, H, I, K, and N, and 200 µm in E, F, and M.