endoteeliin

Endoteeliin, commonly spelled endothelin in English, refers to a family of potent peptide vasoconstrictors produced primarily by vascular endothelium. The three endogenous isoforms—endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3)—are encoded by the EDN1, EDN2 and EDN3 genes. They are synthesized as inactive prepropeptides and activated by endothelin-converting enzymes (ECE-1 and ECE-2) to mature peptides of about 21 amino acids for ET-1, with shorter variants for ET-2 and ET-3.

Endoteeliin exerts its effects by binding to G protein-coupled receptors ETA and ETB. ETA receptors are primarily on vascular smooth muscle and mediate vasoconstriction and proliferation, while ETB receptors are found on endothelial and other cells; endothelial ETB can promote nitric oxide and prostacyclin release, leading to vasodilation, but ETB on smooth muscle can also contribute to constriction. The net vascular effect is context-dependent, varying by vessel bed, receptor expression, and disease state.

Physiological roles include regulation of vascular tone, blood pressure, development, and cell growth; pathologically, endothelin signaling is implicated in pulmonary arterial hypertension, systemic hypertension, heart failure, chronic kidney disease, and fibrotic disorders. Plasma ET-1 levels can serve as a biomarker in some conditions, though interpretation is complex.

Therapeutically, endothelin pathway antagonists are used in several diseases. Endothelin receptor antagonists such as bosentan (dual ETA/ETB), ambrisentan (selective ETA), and macitentan (dual) are approved for pulmonary arterial hypertension and are explored in other conditions. Common adverse effects include liver function disturbance, edema, and anemia. See also endothelin converting enzyme; endothelin receptors; pulmonary arterial hypertension.