BMPR-II | ↓ | Cell apoptosis ↓ Inflammation ↑ | EC, SMC | FK506# indirectly by IL-2 inhibition | + | Animal study, Database study | [30, 42, 43, 44–48] |
Caveolin-1 | ↓ | Cell proliferation ↑ | EC | − | − | Animal study | [39, 43, 49] |
Endothelin-1 | ↑ | Cell apoptosis ↓ Cell proliferation ↑ | EC, SMC, AF | ERA (bosentan, macitentan, ambrisentan) | NA | − | [43, 50] |
HIF-1α | ↑ | Cell proliferation ↑ Cell apoptosis ↓ | EC, SMC, AF | − | + | Animal study | [28, 43, 51] |
IL-6 | ↑ | Inflammation ↑ | EC | Tocilizumab# | +/− | Animal study | [36, 43, 52–54] |
[K+] channels | ↓ | Cell apoptosis ↓ Vasoconstriction ↑ | SMC | − | NA | − | [43, 87, 55] |
MIP-1α | ↑ | Inflammation ↑ | Macrophage | − | NA | − | [43, 56] |
MMP-2 | ↑ | Cell proliferation ↑ | SMC | − | NA | − | [43, 57, 58] |
MT-MMP1 | ↑ | Cell proliferation ↑ | SMC | − | NA | − | [43] |
Nitric oxide | ↓ | Cell proliferation ↑ Clotting ↑ Inflammation ↑ | EC, SMC | PDE5i (sildenafil, tadalafil) Soluble guanylate cyclase stimulators (riociguat) | + | Animal study | [39, 43, 50, 59] |
PDGF | ↑ | Cell proliferation ↑ | EC, SMC, AF | PDGFR inhibitor (imatinib¶) | +/− | Case–control study | [43, 60–62] |
E-selectin | ↑ | Cell proliferation ↑ | EC | − | + | Case–control study | [62] |
P-selectin | ↑ | Cell proliferation ↑ | EC | − | + | Case–control study | [62] |
Prostacyclin | ↓ | Cell proliferation ↑ Clotting ↑ | EC, SMC | Prostacyclin analogues (e.g. epoprostenol, treprostinil) Prostacyclin receptor stimulator (selexipag) | NA | − | [43, 63–65] |
CCL5/RANTES | ↑ | Inflammation ↑ | Macrophage | − | NA | −− | [43, 66] |
TGF-β | ↑ | Cell proliferation ↑ | SMC, AF | | + | Case–control study, human necropsy study, animal study, in vitro study | [31, 32, 35, 38, 40, 43, 67, 68] |
TGF-βR2 | ↓ | Cell apoptosis ↓ Inflammation ↑ | EC, SMC | − | + | in vitro study | [41, 43, 68, 69] |
TIMP-1 | ↑ | Cell proliferation ↑ | SMC | − | NA | − | [43, 57, 70] |
VEGF | ↑ | Cell apoptosis ↓ Cell proliferation ↑ Clotting ↑ Inflammation ↑ | EC, SMC | | + | Animal study | [28, 29, 43, 71] |
vWF | ↑ | Clotting ↑ Inflammation ↑ | EC, SMC | − | NA | − | [43, 72] |
5-HT transporter/ receptor | ↑ | Cell proliferation ↑ Vasoconstriction ↑ | SMC | | NA | − | [44, 73] |