endoteliin1

Endothelin-1 (ET-1) is a peptide hormone produced primarily by vascular endothelial cells. It is the most potent endogenous vasoconstrictor and contributes to the regulation of vascular tone and blood pressure. In addition to constriction, ET-1 promotes smooth muscle proliferation and may participate in inflammatory and fibrotic processes.

ET-1 is synthesized as a larger precursor and is processed to the active 21-amino-acid peptide. Its production is stimulated by factors such as shear stress, hypoxia, angiotensin II, vasopressin, cytokines, and inflammatory stimuli. After release, ET-1 acts locally (paracrine/autocrine) rather than as a circulating hormone in most settings.

Endothelin signals through two receptor subtypes, ETA and ETB. ETA receptors on vascular smooth muscle mediate vasoconstriction and cell growth. ETB receptors on endothelial cells can trigger the release of nitric oxide and prostacyclin, contributing to vasodilation, while ETB receptors on smooth muscle can mediate vasoconstriction in certain beds. The overall vascular effect depends on the balance of receptor expression and signaling context.

Physiologically, ET-1 helps maintain baseline vascular tone and participates in the body’s response to stress. Pathologically, ET-1 levels are elevated in conditions such as pulmonary arterial hypertension, systemic hypertension, heart failure, and atherosclerosis, where it can promote vascular remodeling and fibrosis.

Clinically, endothelin receptor antagonists (ERAs) are used to treat pulmonary arterial hypertension and, in some cases, systemic sclerosis–related interstitial lung disease. Examples include bosentan (dual ETA/ETB antagonism), ambrisentan (selective ETA), and macitentan (dual). Potential adverse effects include liver function abnormalities, edema, and teratogenic risks; monitoring is recommended.

The EDN1 gene encodes the endothelin-1 peptide in humans. Related peptides, endothelin-2 and endothelin-3, have distinct tissue distributions. Research continues into ET-1 as a biomarker and therapeutic target.