Pathophysiological Role in Pulmonary Hypertension

In PAH, circulating and tissue levels of EDN1 are markedly elevated. This excess leads to:

• Chronic Vasoconstriction: Persistent activation of ETA and smooth muscle ETB receptors increases pulmonary arterial tone.
• Vascular Remodeling: EDN1 signaling induces proliferation of smooth muscle cells, fibroblast activation, and extracellular matrix deposition, resulting in arterial thickening and narrowing.
• Inflammation and Fibrosis: Endothelin signaling cross-talks with inflammatory mediators, amplifying fibrosis and endothelial injury.
• Right Ventricular Strain: The sustained increase in pulmonary arterial pressure overloads the right ventricle, driving cardiac hypertrophy and eventual failure.

These mechanisms establish the endothelin axis as a key therapeutic target in PAH.