EndotheliumDerived

Endothelium-derived refers to substances produced by the vascular endothelium, the inner lining of blood vessels, that modulate vascular tone, coagulation, inflammation, and other aspects of circulatory function. Endothelial mediators are released in response to mechanical forces such as shear stress and chemical stimuli including hormones, metabolites, and inflammatory signals. The balance of these factors helps regulate blood flow and blood pressure and maintains vascular homeostasis.

Key endothelium-derived mediators include nitric oxide (NO), prostacyclin (PGI2), endothelin-1 (ET-1), and endothelium-derived hyperpolarizing factor (EDHF). NO, produced by endothelial nitric oxide synthase, diffuses to smooth muscle to promote vasodilation and also inhibits platelet aggregation and leukocyte adhesion. Prostacyclin, generated via the cyclooxygenase pathway, acts as a vasodilator and anti-thrombotic agent. Endothelin-1 is a potent vasoconstrictor that helps regulate vascular tone, often in counterbalance with NO and prostacyclin. EDHF represents a set of mechanisms, not a single compound, that cause hyperpolarization and relaxation of smooth muscle when NO signaling is insufficient or in certain vascular beds.

The concept of endothelium-derived relaxing factor (EDRF) historically referred to the endothelium’s ability to induce vascular relaxation, later understood primarily to involve NO, with contributions from other mediators and EDHF pathways. Endothelial function depends on the proper production and signaling of these mediators.

Endothelial dysfunction occurs when the production or action of protective mediators like NO is reduced or when vasoconstrictors predominate. This state is associated with hypertension, atherosclerosis, diabetes, and chronic inflammation and is often assessed by measures of flow-mediated dilation. Therapeutic strategies aim to improve endothelial function through lifestyle modification and pharmacologic agents that enhance NO signaling, inhibit vasoconstrictors, or support overall vascular health.