Regardless of aetiology PAH patients share common pathological changes to the pulmonary microcirculation (figure 2)^13,14

• vascular hypertrophy and remodelling
• intimal fibrosis
• inflammation
• pulmonary vasoconstriction

Figure 2: PAH is a disease of cellular proliferation and occlusion of pulmonary arteries¹⁵

Endothelin

• Endothelin is a key pathogenic mediator in PAH, produced primarily by vascular endothelial cells¹⁶
• Excess endothelin has diverse deleterious effects and results in pulmonary arteriopathy (figure 3)¹⁷
  • vasoconstriction
  • inflammation
  • fibrosis
  • vascular hypertrophy

Figure 3: ET deleterious effects in PAH¹⁷

• Both ET_A & ET_B receptors are implicated in PAH (figure 4)^18-22

Figure 4: Both ET_A and ET_B receptors mediate the deleterious effects of ET in PAH²²

• Endothelin levels are elevated in PAH of multiple aetiologies (Figure 5)^23-25
  

Figure 5: Endothelin levels in different forms of PAH^23-25

• Endothelin levels are strongly correlated with severity of PAH and prognosis (figure 6)²⁶

Figure 6: Correlation between ET plasma levels and survival in PAH²⁶

• Endothelin-mediated cardiopulmonary vascular and structural changes accompany disease progression in PAH