Control | PAH | CTEPH | PH-HFpEF | PH-HFrEF | Non-PH-HF | |
TAM receptor kinase family | ||||||
MERTK | 3.58 (3.47–3.90) | 4.05 (3.82–4.36)# | 4.32 (4.12–4.56)# | 4.37 (4.13–4.62)# | 4.15 (3.89–4.68)# | 4.33 (4.19–4.57)# |
AXL | 7.35 (7.18–7.63) | 7.35 (6.93–7.65) | 7.23 (7.03–7.43) | 7.47 (7.20–8.02) | 7.68 (7.38–8.05)¶,+ | 7.50 (7.23–8.01) |
VEGF family | ||||||
VEGFR-2 | 6.58 (6.38–6.68) | 6.18 (5.96–6.41)# | 6.18 (6.02–6.40)# | 6.01 (5.86–6.18)# | 6.18 (5.99–6.32)# | 6.10 (5.88–6.34)# |
VEGFR-3 | 5.74 (5.42–5.79) | 5.74 (5.51–5.92) | 5.80 (5.55–5.95) | 5.77 (5.51–5.91) | 5.88 (5.74–6.06)#,¶ | 5.73 (5.49–5.96) |
VEGF-A | 9.13 (8.94–9.43) | 9.83 (9.45–10.22)# | 9.87 (9.61–10.54)# | 10.02 (9.78–10.45)# | 9.76 (9.37–10.18)# | 9.77 (9.45–10.02)# |
VEGF-D | 6.78 (6.56–6.92) | 7.23 (7.01–7.48)# | 7.47 (7.24–7.66)# | 7.47 (7.20–7.74)# | 7.97 (7.74 –8.05)#,¶,+,§ | 7.36 (6.65–7.74)ƒ |
PlGF | 6.92 (6.78–7.26) | 7.61 (7.43–8.08)# | 7.64 (7.46–7.93)# | 7.92 (7.57–8.31)# | 7.62 (7.31–8.03)# | 7.72 (7.42–7.89)# |
EGF family | ||||||
EGFR | 1.38 (1.26–1.56) | 0.82 (0.65–1.08)# | 1.04 (0.82–1.10)# | 0.99 (0.73–1.15)# | 1.08 (0.97–1.23)#,¶ | 1.06 (0.92–1.24)# |
HER2 | 6.44 (6.20–6.69) | 6.39 (6.09–6.55) | 6.54 (6.37–6.72) | 6.43 (6.16–6.71) | 6.72 (6.63–6.92)#,¶,§ | 6.68 (6.47–6.74) |
HER3 | 7.46 (7.31–7.54) | 7.26 (7.11–7.44) | 7.42 (7.27–7.63) | 7.32 (7.08–7.38) | 7.37 (7.20–7.62) | 7.30 (7.20–7.56) |
HER4 | 4.55 (4.24–4.65) | 4.50 (4.36–4.66) | 4.56 (4.38–4.67) | 4.48 (4.33–4.68) | 4.80 (4.63–5.00)#,¶,§ | 4.76 (4.27–4.93) |
Pro-EGF | 8.63 (7.36–9.48) | 7.76 (6.57–8.62) | 7.96 (6.84–8.61) | 7.97 (7.16–8.85) | 7.12 (5.93–8.05)# | 7.85 (7.25–8.96) |
Amphiregulin | 1.43 (1.21–1.57) | 2.43 (2.09–2.79)# | 2.14 (1.99–2.49)# | 2.30 (1.99–2.83)# | 2.62 (2.02–3.15)# | 1.99 (1.76–2.61)# |
HB-EGF | 5.90 (5.44–6.33) | 5.77 (5.53–6.24) | 6.52 (5.84–6.98)¶ | 6.13 (5.57–6.48) | 5.75 (5.37–6.17)+ | 6.28 (5.75–6.70) |
TGF-α | 1.20 (0.93–1.39) | 1.82 (1.62–2.15)# | 2.07 (1.60–2.37)# | 2.05 (1.67–2.48)# | 2.06 (1.77–2.35)# | 1.56 (1.48–2.09)# |
TIE family of angiopoietin receptors | ||||||
Tie2 | 7.53 (7.35–7.64) | 7.57 (7.40–7.82) | 7.81 (7.59–7.98)# | 7.72 (7.57–7.97) | 8.09 (7.79–8.17)#,¶,§ | 7.90 (7.60–8.11)# |
Ang-1 | 8.26 (7.68–8.97) | 8.27 (7.84–9.03) | 9.20 (8.09–9.75) | 8.57 (7.87–9.36) | 8.11 (7.32–8.81)+ | 9.00 (7.89–9.50) |
PDGF family | ||||||
PDGF subunit A | 2.89 (2.41–3.40) | 2.89 (2.04–3.36) | 3.57 (3.01–4.63) | 3.12 (2.09–3.77) | 2.70 (2.16–3.42)+ | 3.22 (2.30–3.90) |
PDGF subunit B | 9.48 (8.65–9.92) | 9.17 (8.52–9.77) | 9.55 (8.94–10.16) | 9.50 (8.27–9.83) | 8.82 (7.87–9.54) | 9.45 (8.66–9.98) |
Non-RTK family | ||||||
SRC | 6.87 (6.77–7.11) | 6.93 (6.51–7.17) | 6.82 (6.52–7.12) | 6.96 (6.68–7.14) | 6.88 (5.95–7.22) | 7.12 (6.64–7.28) |
LYN | 2.80 (2.13–3.21) | 2.38 (1.89–2.97) | 2.30 (2.11–2.54) | 2.49 (2.17–3.11) | 2.28 (1.87–2.75) | 2.48 (2.13–3.32) |
ABL-1 | 4.57 (3.05–5.31) | 3.87 (3.24–4.99) | 4.15 (3.93–4.71) | 4.57 (4.08–5.33)¶ | 4.11 (3.71–4.88) | 4.88 (4.04–5.37) |
Ephrin receptor family | ||||||
EPHA2 | 1.50 (1.39–1.59) | 1.89 (1.63–2.18)# | 1.69 (1.52–1.97) | 2.10 (1.83–2.38)# | 1.67 (1.48–2.24)# | 1.81 (1.70–2.10)# |
EPHB4 | 1.44 (1.29–1.54) | 1.50 (1.13–1.77) | 1.54 (1.39–1.65) | 1.72 (1.46–2.02)#,¶ | 1.72 (1.41–1.89) | 1.62 (1.36–1.68) |
Other tyrosine kinases | ||||||
RET | 3.96 (3.59–4.32) | 3.13 (2.77–3.53)# | 3.75 (3.37–4.12)¶ | 3.58 (3.36–3.91)¶ | 3.71 (3.30–4.19)¶ | 3.73 (3.4–4.16)¶ |
SCF | 8.45 (8.34–8.80) | 8.01 (7.37–8.36)# | 8.29 (8.00–8.68) | 8.26 (7.78–8.48) | 7.72 (7.31–8.08)#,+,§ | 8.11 (7.71–8.46) |
HGF | 5.50 (5.24–5.85) | 6.35 (6.18–6.66)# | 6.54 (6.06–6.81)# | 6.66 (6.20–7.02)# | 6.59 (6.33–7.38)# | 6.60 (6.13–7.22)# |
FGF-BP1 | 4.30 (4.19–4.34) | 4.59 (4.38–4.89)# | 4.61 (4.36–4.72) | 4.5 (4.33–4.81) | 4.83 (4.40–5.19)# | 4.49 (4.26–4.81) |
Levels are presented as median (interquartile range) of arbitrary units. PAH: pulmonary arterial hypertension; CTEPH: chronic thromboembolic pulmonary hypertension; PH-HFpEF: pulmonary hypertension due to diastolic heart failure (preserved ejection fraction); PH-HFrEF: pulmonary hypertension due to systolic heart failure (reduced ejection fraction); non-PH-HF: heart failure without pulmonary hypertension; MERTK: tyrosine-protein kinase MER; AXL: tyrosine-protein kinase receptor UFO; VEGF: vascular endothelial growth factor; VEGFR: VEGF receptor; PlGF: placental growth factor; pro-EGF: pro-epidermal growth factor; EGFR: EGF receptor; HER: human EGFR; HB-EGF: heparin-binding EGF-like growth factor; TGF: transforming growth factor; Tie2: angiopoietin receptor TEK tyrosine kinase; Ang-1: angiopoietin 1; PDGF: platelet-derived growth factor; RTK: receptor tyrosine kinase; SRC: proto-oncogene tyrosine-protein kinase Src; LYN: tyrosine-protein kinase Lyn; ABL-1: tyrosine-protein kinase ABL1; EPHA2: ephrin type A receptor 2; EPHB4: ephrin type B receptor 4; RET: proto-oncogene tyrosine-protein kinase receptor Ret; SCF: stem cell factor; HGF: hepatocyte growth factor; FGF-BP1: fibroblast growth factor-binding protein 1. #: significantly different compared with controls; ¶: significantly different compared with PAH; +: significantly different compared with CTEPH; §: significantly different compared with PH-HFpEF; ƒ: significantly different compared with PH-HFrEF.