Endothelial Function

The endothelium is a tissue regulating vascular tone, cell growth, and the interaction between leukocytes, thrombocytes, and the vessel wall. ^[1] Endothelial cells form the inner linings of blood vessels and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. ^[2] The term endothelial dysfunction is generally used for deterioration of endothelium-dependent vasodilatation. ^[1]

The endothelium modulates vascular tone by synthesizing and releasing a variety of endothelium-derived relaxing factors, including vasodilator prostaglandins, nitric oxide, and endothelium-dependent hyperpolarization factors. ^[3] Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. ^[4] Causes of endothelial dysfunction include oxidative stress, inflammation, and shear stress, which decrease the bioavailability of nitric oxide. ^[5]

Endothelial function declines with age, most obvious from the attenuation of endothelium-dependent dilator responses, which is a consequence of altered expression or activity of the endothelial NO synthase and increased formation of reactive oxygen species. ^[6] Large elastic artery stiffening and endothelial dysfunction are two major age-related arterial phenotypes that are independent predictors of future cardiovascular disease diagnosis. ^[7] The senescence and death of endothelial cells are causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. ^[2]

Because endothelial function plays a central role in atherogenesis it became a therapeutic target, and endothelial dysfunction is reversible so that reversing it can restore vascular function. ^[5] In a meta-analysis of randomized controlled trials, flavan-3-ol interventions increased flow-mediated dilation after acute and repetitive consumption independent of blood pressure. ^[8] Improvement of endothelial dysfunction may be achieved by elimination of risk factors, smoking cessation, lipid-lowering drugs, diet, and physical exercise. ^[5]