Table 2.
Time course of mRNA expression in cultured myocardium
| Function and protein | Gene | 8 days | 14 days | 24 days | 35 days | Intercept | Slope x35 |
|---|---|---|---|---|---|---|---|
| Growth factors | |||||||
| Growth differentiation factor 15 | GDF15 | 2.98 | 2.07 | 2.26 | 1.32 | 3.19 | −1.79 |
| Hepatocyte growth factor | HGF | 2.21 | 3.12 | 2.66 | 3.17 | 2.30 | 0.84 |
| Opioid growth factor rec. like 1 | OGFRL1 | 1.16 | 2.20 | 0.91 | 2.00 | 1.33 | 0.41 |
| Platelet derived growth factor receptor beta | PDGFRB | 1.34 | 3.66 | 1.93 | 3.56 | 1.64 | 1.70 |
| Placental growth factor | PGF | 3.06 | 4.20 | 2.42 | 3.65 | 3.38 | −0.08 |
| Transforming growth factor beta 1 | TGFB1 | 1.69 | 2.75 | 1.76 | 2.22 | 2.04 | 0.12 |
| Angiotensin I converting enzyme | ACE | 1.87 | 3.02 | 1.94 | 2.05 | 2.43 | −0.36 |
| Extracellular matrix | |||||||
| Collagen type I alpha 1 chain | COL1A1 | 3.16 | 4.04 | 2.90 | 3.86 | 3.31 | 0.32 |
| Collagen type I alpha 2 chain | COL1A2 | 2.42 | 3.19 | 2.20 | 3.36 | 2.40 | 0.68 |
| Collagen type III alpha 1 chain | COL3A1 | 2.25 | 3.30 | 2.50 | 3.52 | 2.26 | 1.09 |
| Vimentin | VIM | 0.96 | 1.70 | 1.25 | 1.21 | 1.27 | 0.02 |
| Laminin subunit gamma 1 | LAMC1 | 0.87 | 1.45 | 0.30 | 1.77 | 0.73 | 0.63 |
| Periostin | POSTN | 2.70 | 3.48 | 1.92 | 3.44 | 2.73 | 0.26 |
| Fibronectin 1 | FN1 | 3.24 | 3.89 | 2.41 | 3.35 | 3.49 | −0.46 |
| Hypoxia-induced targets | |||||||
| Vascular endothelial growth factor A | VEGFA | −0.59 | 1.18 | −0.98 | −0.38 | 0.26 | −0.78 |
| Solute carrier family 2 member 1 | SLC2A1 | −1.97 | 1.79 | −1.30 | −0.12 | −0.70 | 0.53 |
| Glyceraldehyde-3-phosphate dehydrogenase | GAPDH | −0.20 | −0.19 | −0.24 | −1.02 | 0.18 | −1.02 |
| Protein kinase, cAMP-activated | PRKACA | −0.33 | −0.78 | −1.11 | −0.62 | −0.50 | −0.37 |
| Phosphoglycerate kinase 1 | PGK1 | −0.85 | 0.18 | −0.80 | −0.94 | −0.24 | −0.63 |
| Positive trend | |||||||
| Elastin | ELN | −2.68 | −1.10 | −0.75 | 2.12 | −3.88 | 5.67 |
| Nerve growth factor receptor | NGFR | −1.80 | 2.04 | 0.91 | 3.71 | −2.03 | 5.61 |
| Kelch-like family member 38 | KLHL38 | −3.53 | −0.90 | −1.16 | 1.48 | −4.22 | 5.52 |
| X-prolyl aminopeptidase 2 | XPNPEP2 | −1.77 | 2.22 | 1.05 | 3.65 | −1.87 | 5.45 |
| Integrin subunit beta like 1 | ITGBL1 | −2.75 | 0.02 | −0.20 | 2.16 | −3.30 | 5.38 |
| Neurotrophic receptor tyrosine kinase 2 | NTRK2 | −1.88 | −0.43 | −0.61 | 2.45 | −2.98 | 4.95 |
| Phospholipid phosphatase rel. 4 | LPPR4 | −0.39 | 0.67 | 2.76 | 2.60 | −0.96 | 4.10 |
| Negative trend | |||||||
| Prolyl 4-hydroxylase alpha 3 | P4HA3 | 3.61 | 4.06 | 2.55 | 0.40 | 5.26 | −4.51 |
| Interleukin 6 | IL6 | 2.56 | 1.20 | 1.13 | −1.18 | 3.43 | −4.33 |
| TNF receptor superfamily member 12 A | TNFRSF12A | 2.71 | −1.30 | −0.96 | −1.48 | 2.18 | −4.21 |
| Cell division cycle associated 2 | CDCA2 | 1.94 | 0.23 | −0.48 | −1.50 | 2.41 | −4.08 |
| Wnt family member 5 A | WNT5A | 2.90 | 1.19 | 0.20 | −0.21 | 3.20 | −3.77 |
| Protein phosphatase 1 regulatory subunit 16 B | PPP1R16B | 0.21 | −0.31 | −2.56 | −2.36 | 0.91 | −3.75 |
| C-X-C motif chemokine ligand 1 | CXCL1 | 3.15 | 1.10 | 0.25 | 0.02 | 3.26 | −3.68 |
Gene expression reflecting myocardial remodelling during tissue culture. The ratios of gene transcripts in cultured vs. uncultured tissue from the same patient are expressed as Log2-values. Temporal alterations of gene expression were approximated by linear regression of all culture durations. This calculation estimated the change of expression levels at the start of cultivation (intercept), and the temporal trend during 35 days of culture (slope ×35). Genes were selected that represent typical culture-related alterations, such as cell proliferation and hypoxia. Exemplary genes are also shown that underwent most extensive induction or downregulation in the course of biomimetic culture (positive or negative trends). Complete mRNA expression data are provided as Supplementary Data 1