Endothelial dysfunction

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Endothelial dysfunction is a physiological dysfunction of normal biochemical processes carried out by the endothelium, the cells that line the inner surface of all blood vessels including arteries and veins (as well as the innermost lining of the heart and lymphatics.) Compromise of normal function of endothelial cells is characteristic of endothelial dysfunction. Normal functions of endothelial cells include mediation of coagulation, platelet adhesion, immune function, control of volume and electrolyte content of the intravascular and extravascular spaces. Endothelial dysfunction can result from disease processes, as occurs in septic shock, hypertension, hypercholesterolaemia, diabetes as well as from environmental factors, such as from smoking tobacco products.

Endothelial dysfunction is thought to be a key event in the development of atherosclerosis and predates clinically obvious vascular pathology by many years. Endothelial dysfunction has also been shown to be of prognostic significance in predicting vascular events including stroke and heart attacks.

A key feature of endothelial dysfunction is the inability of arteries and arterioles to dilate fully in response to an appropriate stimulus. This can be tested by a variety of methods including iontophoresis of acetylcholine, intra-arterial administration of various vasoactive agents, localised heating of the skin and temporary arterial occlusion by inflating a blood pressure cuff to high pressures. Testing can also take place in the coronary arteries themselves but this is invasive and not normally conducted unless there is a clinal reason for intracoronary catheterisation. These techniques are thought to stimulate the endothelium to release nitric oxide (NO) and possibly some other agents, which diffuse into the surrounding vascular smooth muscle causing vasodilation.

Dysfunctional endothelial cells are unable to produce NO to the same extent (or there is increased and rapid destruction of NO) as healthy endothelial cells and therefore vasodilatation is reduced. This creates a detectable difference in subjects with endothelial dysfunction verses a normal, healthy endothelium.

Unfortunately the variability in such tests means that no technique has yet been identified that would allow endothelial testing to attain routine clinical significance.

As more research is conducted to improve testing methodologies for endothelial dysfunction, however, several non-invasive tests have been created by various medical-research companies.^[1]

Endothelial function can be improved significantly by exercise and improved diet. A study published in 2005 has determined that a positive relationship exists between the consumption of trans fat (commonly found in hydrogenated products such as margarine) and the development of endothelial dysfunction.^[2] Other factors have been identified as improving endothelial function and include cessation of smoking, loss of weight and treatment of hypertension and hypercholesterolemia amongst other things.

Endothelial dysfunction has been observed in a 2001 study of women where it was found that this disorder is present in approximately half of women with chest pain, in the absence of overt blockages in large coronary arteries. This endothelial dysfunction cannot be predicted by typical risk factors for atherosclerosis (e.g., obesity, cholesterol, smoking) and hormones. ^[3]

[edit] References

^ Endothelial dysfunctionat Itamar Medical
^ Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB, "Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction", Journal of Nutrition, Mar 2005;135(3):562-6.
^ Reis SE, Holubkov R, Smith AJC, Kelsey SF, Sharaf BL, Reichek N, Rogers WJ, Merz NB, Sopko G, Pepine CJ, “Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: Results from the NHLBI WISE Study,” Am Heart J, V. 141, No. 5 (May 2001), pp. 735-741