Endothelien

Endothelien are a family of potent vasoactive peptides produced mainly by vascular endothelial cells. The best studied member is Endothelin-1 (ET-1); two other isoforms, Endothelin-2 (ET-2) and Endothelin-3 (ET-3), are expressed in various tissues. Endothelien act as strong vasoconstrictors and as mitogens, influencing vascular tone, cellular proliferation, and remodeling.

Biosynthesis: They are synthesized as preproendothelin, processed to proendothelin and then to big endothelin, which is cleaved by endothelin-converting enzyme (ECE) to the active peptides. ET-1 is the predominant and most biologically active isoform; ET-2 and ET-3 have tissue-specific expression patterns.

Receptors and signaling: Endothelien exert their effects primarily via two G protein-coupled receptors, ETA and ETB. ETA receptors are mainly on vascular smooth muscle and promote vasoconstriction and proliferation. ETB receptors on endothelial cells trigger release of nitric oxide and prostacyclin, contributing to vasodilation and endothelin clearance; ETB receptors on some smooth muscle can mediate constriction.

Physiological role: The endothelin system helps regulate vascular tone, systemic and renal hemodynamics, and pulmonary circulation. It also participates in development, angiogenesis, and tissue remodeling under physiological and pathological conditions.

Clinical relevance: Increased endothelin signaling has been linked to cardiovascular diseases, notably pulmonary arterial hypertension, systemic hypertension, and heart failure. Therapeutic antagonists of endothelin receptors are used in PAH management (for example bosentan, ambrisentan, macitentan), and research continues into broader applications.

Measurement and regulation: Plasma endothelin-1 levels can reflect vascular endothelium activity and are influenced by hypoxia, shear stress, and inflammation. Endothelin clearance is mediated in part by ETB receptors; dysregulation can contribute to disease.