Table 3.
Proteins’ alterations in controls and patients before and 1-year after heart transplantation
| Protein (AU) | Control (n = 20) | Pre-HT (n = 26) | Post-HT (n = 26) | Δ (Post-HT)–(Pre-HT) (n = 26) | p value | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| n | Median (IQR) | n | Median (IQR) | n | Median (IQR) | n | Median (IQR) | Pre-HT vs. C | Post-HT vs. C | Post vs. Pre-HT | |
| NT-proBNP | 20 | 1.1 (1.1–1.2) | 26 | 24 (11–40) | 26 | 2 (1.4–5.8) | 26 | − 17 (− 37 to − 8.4) | 3.6 × 10−13* | 5.0 × 10−5* | 3.0 × 10−8* |
| VEGF family | |||||||||||
| PDGF-A | 20 | 7.4 (5.3–11) | 26 | 7.4 (4.5–11) | 26 | 5.2 (3.5–8.3) | 26 | − 1.4 (− 5.4 to 1.1) | 0.82 | 0.055 | 0.071 |
| PDGF-B | 20 | 716 (404–965) | 26 | 506 (228–802) | 26 | 337 (220–707) | 26 | − 11 (− 289 to 239) | 0.078 | 0.023 | 0.92 |
| PlGF | 20 | 120 (110–154) | 26 | 188 (157–217) | 26 | 203 (168–265) | 26 | 14 (− 21 to 56) | 2.6 × 10−6* | 2.1 × 10−9* | 0.32 |
| VEGF-A | 19 | 562 (490–692) | 25 | 798 (666–1061) | 26 | 847 (709–999) | 25 | − 14 (− 174 to 170) | 4.7 × 10−5* | 5.7 × 10−6* | 0.65 |
| VEGF-D | 20 | 110 (94–121) | 26 | 243 (199–262) | 26 | 126 (92–163) | 26 | − 118 (− 153 to − 49) | 5.0 × 10−8* | 0.17 | 4.2 × 10−7* |
| VEGFR-2 | 19 | 96 (83–103) | 25 | 72 (60–79) | 26 | 73 (60–82) | 25 | − 0.3 (− 6.6 to 6) | 3.7 × 10−5* | 2.8 × 10−5* | 0.99 |
| VEGFR-3 | 19 | 53 (43–55) | 25 | 59 (53–66) | 26 | 44 (39–49) | 25 | − 16 (− 18 to − 9.2) | 0.0051* | 0.020 | 6.0 × 10−8* |
| EGF family | |||||||||||
| Amphiregulin | 19 | 2.7 (2.3–3) | 25 | 5.4 (4–9.6) | 26 | 4.1 (3.5–5.2) | 25 | − 1 (− 5 to 0.41) | 1.3 × 10−9* | 1.7 × 10−7* | 0.020 |
| EGFR | 20 | 2.6 (2.4–2.9) | 26 | 2.2 (2–2.4) | 26 | 1.9 (1.8–2) | 26 | − 0.28 (− 0.45 to − 0.079) | 0.0012* | 0.011 | 0.045 |
| HER2 | 19 | 87 (74–103) | 25 | 106 (100–119) | 26 | 79 (70–86) | 25 | − 30 (− 43 to − 20) | 1.7 × 10−5* | 6.8 × 10−12* | 7.5 × 10−6* |
| HER3 | 19 | 177 (158–186) | 25 | 172 (151–195) | 26 | 170 (147–189) | 25 | − 6.2 (− 21 to 10) | 0.64 | 0.385 | 0.84 |
| HER4 | 19 | 23 (19–25) | 25 | 29 (25–32) | 26 | 20 (17–21) | 25 | − 9 (− 12 to − 5.7) | 0.00021* | 0.087 | 1.2 × 10−7* |
| EGF | 19 | 395 (164–713) | 25 | 132 (54–265) | 26 | 163 (77–373) | 25 | 42 (− 22 to 143) | 0.80 | 0.67 | 0.30 |
| HB-EGF | 20 | 60 (43–81) | 26 | 54 (41–77) | 26 | 49 (43–74) | 26 | − 0.85 (− 17 to 14) | 0.00014* | 0.0088 | 1.2 × 10−7* |
| TGF-α | 19 | 2.3 (1.9–2.6) | 25 | 4.2 (3.7–4.9) | 26 | 3.7 (2.9–4.2) | 25 | − 0.63 (− 1.6 to 0.24) | 6.4 × 10−9* | 6.7 × 10−7* | 0.0051* |
| TAM family | |||||||||||
| AXL | 20 | 163 (145–198) | 26 | 197 (164–249) | 26 | 187 (166–261) | 26 | 5.8 (− 47 to 29) | 0.021 | 0.012 | 0.82 |
| MERTK | 20 | 12 (11–15) | 26 | 18 (14–24) | 26 | 16 (14–20) | 26 | − 1.2 (− 5 to 3.3) | 3.1 × 10−5* | 8.5 × 10−5* | 0.15 |
| TEK family | |||||||||||
| Angiopoietin-1 | 20 | 306 (205–502) | 26 | 295 (160–587) | 26 | 213 (154–503) | 26 | − 38 (− 179 to 121) | 0.80 | 0.31 | 0.58 |
| Tie-2 | 20 | 185 (164–199) | 26 | 273 (241–289) | 26 | 184 (158–203) | 26 | − 87 (− 107 to − 67) | 1.9 × 10−8* | 0.97 | 6.0 × 10−8* |
| Ephirns | |||||||||||
| EphA2 | 19 | 2.8 (2.6–3) | 25 | 3.1 (2.8–4) | 26 | 4.2 (3–5) | 25 | 0.37 (− 0.03 to 1.3) | 0.019 | 6.5 × 10−5* | 0.019 |
| EphB4 | 20 | 2.7 (2.4–2.9) | 26 | 3 (2.5–3.7) | 26 | 3.1 (2.5–3.7) | 26 | − 0.29 (− 0.65 to 0.2) | 0.078 | 0.082 | 0.23 |
| Intracellular TK | |||||||||||
| ABL1 | 19 | 24 (8.3–40) | 25 | 17 (11–29) | 26 | 18 (13–28) | 25 | 1.4 (− 9.4 to 8.5) | 0.76 | 0.62 | 0.79 |
| LYN | 19 | 6.9 (4.4–9.3) | 25 | 5 (3.3–6.5) | 26 | 4.8 (3.1–6.9) | 25 | 0.16 (− 2.2 to 1.6) | 0.11 | 0.044 | 0.77 |
| SRC | 20 | 117 (109–138) | 26 | 105 (52–147) | 26 | 110 (68–162) | 26 | 12 (− 18 to 46) | 0.24 | 0.66 | 0.25 |
| Other TK | |||||||||||
| FGF-BP1 | 19 | 20 (18–20) | 25 | 27 (19–36) | 26 | 20 (17–22) | 25 | − 7.3 (− 14 to − 0.31) | 0.0032* | 0.97 | 0.00010* |
| HGF | 19 | 45 (38–58) | 25 | 110 (91–176) | 26 | 58 (47–74) | 25 | − 59 (− 109 to − 29) | 2.8 × 10−10* | 0.014 | 1.2 × 10−7* |
| RET | 19 | 16 (12–20) | 25 | 14 (10–19) | 26 | 12 (8.7–14) | 25 | − 1.4 (− 5.8 to − 0.23) | 0.54 | 0.0094 | 0.0096 |
| SCF | 19 | 349 (324–446) | 25 | 216 (161–263) | 26 | 385 (343–428) | 25 | 189 (86 to 237) | 8.4 × 10−6* | 0.53 | 6.0 × 10−8* |
Plasma proteins were grouped according to receptors and associated ligands into: vascular endothelial growth factor (VEGF family); epidermal growth factor (EGF family); TAM receptor kinase (TAM-family); TIE angiopoietin receptor (TEK family); TK, tyrosine kinase. (Δ) Plasma level development following HT
HT heart transplantation, C control, IQR interquartile range. Proteins: PDGF-A platelet-derived growth factor subunit-A, PDGF-B platelet-derived growth factor subunit B, PlGF placenta growth factor, VEGFR-2 and 3 VEGF receptor 2, 3, EGF pro-epidermal growth factor, EGFR epidermal growth factor receptor, HB-EGF proheparin-binding EGF-like growth factor, HER2, 3 and 4 human epidermal growth factor receptor 2, 3, 4, TGF-α transforming growth factor alpha, Tie-2 angiopoietin-1 receptor, EphA2 ephrin type-A receptor 2, EphB4 ephrin type-B receptor 4, ABL1 tyrosine-protein kinase ABL1, LYN tyrosine-protein kinase Lyn, SRC proto-oncogene tyrosine-protein kinase Src, FGF-BP1 fibroblast growth factor-binding protein 1, HGF hepatocyte growth factor, RET proto-oncogene tyrosine-protein kinase receptor Ret, SCF stem cell factor
*p < 0.01, FDR < 0.01