Endothelial dysfunction

Endothelial dysfunction is a pathological state in which the inner lining of blood vessels — the endothelium — fails to maintain normal vascular homeostasis, most characteristically through impaired synthesis or bioavailability of nitric oxide (NO), the principal vasodilatory and anti-inflammatory signaling molecule produced by endothelial nitric oxide synthase (eNOS). Mechanical shear stress from blood flow normally activates eNOS, releasing NO that diffuses into vascular smooth muscle to cause relaxation; in dysfunctional endothelium this response is blunted because reactive oxygen species — particularly superoxide — scavenge NO before it can act, and because eNOS itself becomes uncoupled, generating oxidant rather than NO. The standard clinical measure is flow-mediated dilation (FMD) of the brachial artery, a non-invasive ultrasound technique first validated by Celermajer et al. (1992): reactive-hyperaemia cuff inflation triggers shear stress, and the percentage increase in arterial diameter reflects endothelium-dependent, NO-mediated vasodilation. Beyond impaired vasodilation, dysfunctional endothelium promotes adhesion molecule expression, leukocyte recruitment, platelet activation, and a pro-thrombotic surface — recognized as an early step in atherosclerotic plaque formation preceding overt luminal narrowing by years or decades (Bonetti et al., 2003). FMD declines with age even in healthy individuals, and prospective data show that lower FMD independently predicts major cardiovascular events; whether therapeutically restoring FMD reduces event rates remains under active investigation.