Human endothelial dysfunction: EDCFs

Abstract

Human studies, conducted in the presence of clinical conditions characterized by endothelial dysfunction, evidenced that endothelial cells, in response to different agonists and physical stimuli, become a source of endothelium-derived contracting factors (EDCFs), mainly cyclooxygenase (COX)-derived prostanoids. Their production has been documented in several human diseases, mostly in essential hypertension and aging. The EDCF production was at first identified as responsible for impaired endothelium-dependent vasodilation in the forearm microcirculation of patients with essential hypertension. Subsequent studies demonstrated that COX-dependent EDCF products are also a characteristic of the aging process, and essential hypertension seems to only anticipate the phenomenon. Of note, in aging and hypertension, both indomethacin, a COX inhibitor, and vitamin C, an antioxidant, totally reverse the blunted vasodilation to acetylcholine by restoring NO availability, thus suggesting that EDCFs could be one of the major sources of oxygen free radicals. The presence of EDCFs was documented also in other clinical setting, such as coronary artery disease and estrogen deprivation. In conclusion, many human pathological conditions characterized by a decline in endothelial function are associated with a progressive decrease in NO bioavailability and increase in the production of EDCFs. The mechanisms that regulate the balance between NO and EDCFs and the processes transforming the endothelium from a protective organ to a source of vasoconstrictor, proaggregatory and promitogenic mediators, remain to be determined.

Childhood obesity–related endothelial dysfunction: an update on pathophysiological mechanisms and diagnostic advancements

“…In response to stimuli for increased blood flow demand, endothelial nitric oxide synthase in endothelial cells is activated and produces nitric oxide, which diffuses into the vessel wall to fine-tune vasodilation (3). Although nitric oxide is considered a key regulator of endothelial function, several other factors are involved as well (4,5). The location of the endothelium close to the blood circulation, however, exposes the endothelial cells to many damaging factors.…”

Endothelial Dysfunction in Small Arteries of Essential Hypertensive Patients

“…In genetic hypertension, a number of endothelium-derived contracting factors have been identified. These include several prostanoids, such as prostaglandins and thromboxane A 2 , derived from arachidonic acid by the enzyme cyclooxygenase (COX), and reactive oxygen species (ROS), 1,2 generated by several enzymatic sources, including nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase, xanthine oxidase (XO), uncoupled NO synthase (NOS), or COXs itself. 3 Pivotal studies in animal models of genetic hypertension have demonstrated an evident production of COX-dependent endothelium-derived contracting factors accounting for endothelial dysfunction.…”

Etiopathology of Type 1 Diabetes: Focus on the Vascular Endothelium

“…(Versari et al, 2009). The dysfunctioning endothelium may produce other substances and mediators such as endothelin 1, thromboxane A 2 , prostaglandin H and reactive oxygen species, with vasoconstricting, pro-inflammatory, and proatherosclerotic effects (Virdis et al, 2010). Given the excess of inflammatory and oxidative stress in type 1 diabetes, the endothelium in individuals with type 1 diabetes is continually exposed to factors promoting the development of endothelial dysfunction.…”