TABLE 2

Biomarker plasma levels

ControlPAHCTEPHPH-HFpEFPH-HFrEFNon-PH-HF
TAM receptor kinase family
 MERTK3.58 (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)#
 AXL7.35 (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-26.58 (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-35.74 (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-A9.13 (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-D6.78 (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
 PlGF6.92 (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
 EGFR1.38 (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)#
 HER26.44 (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)
 HER37.46 (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)
 HER44.55 (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-EGF8.63 (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)
 Amphiregulin1.43 (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-EGF5.90 (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-α1.20 (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
 Tie27.53 (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-18.26 (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 A2.89 (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 B9.48 (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
 SRC6.87 (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)
 LYN2.80 (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-14.57 (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
 EPHA21.50 (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)#
 EPHB41.44 (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
 RET3.96 (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)
 SCF8.45 (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)
 HGF5.50 (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-BP14.30 (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.