Endothelial dysfunction
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Endothelial dysfunction is a systemic pathological state of the endothelium (the inner lining of blood vessels) and can be broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by (or acting on) the endothelium.[1] Normal functions of endothelial cells include mediation of coagulation, platelet adhesion, immune function and control of volume and electrolyte content of the intravascular and extravascular spaces. Endothelial dysfunction can result from and/or contribute to several disease processes, as occurs in septic shock, hypertension, hypercholesterolaemia, diabetes, it can also result from environmental factors, such as from smoking tobacco products and exposure to air pollution.
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[edit] Atherosclerosis
Endothelial dysfunction is thought to be a key event in the development of atherosclerosis and predates clinically obvious vascular pathology by many years. This is because endothelial dysfunction is associated with reduced anticoagulant properties as well as increased adhesion molecule expression, chemokine and other cytokine release, and reactive oxygen species production from the endothelium, all of which play important roles in the development of atherosclerosis. In fact, endothelial dysfunction has been shown to be of prognostic significance in predicting vascular events including stroke and heart attacks. Because of this, endothelial function testing may have great potential prognostic value for the detection of cardiovascular disease, but currently the available tests are too difficult, expensive, and/or variable for routine clinical use.
[edit] NO bioavailability
A key and quantifiable feature of endothelial dysfunction is the inability of arteries and arterioles to dilate fully in response to an appropriate stimulus that stimulates release of vasodilators from the endothelium like nitric oxide (NO). Endothelial dysfunction is commonly associated with decreased NO bioavailability, which is due to impaired NO production by the endothelium and/or increased inactivation of NO by reactive oxygen species.This can be tested by a variety of methods including iontophoresis of acetylcholine, direct administration of various vasoactive agents to segments of blood vessels, 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 clinical reason for intracoronary catheterisation. Of all the current tests employed in the research setting, flow-mediated dilation is the most widely used non-invasive test for assessing endothelial function. This technique measures endothelial function by inducing reactive hyperemia via temporary arterial occlusion and measuring the resultant relative increase in blood vessel diameter via ultrasound. As people with endothelial dysfunction have low NO bioavailability, their blood vessels have a decreased capacity to dilate in response to certain stimuli, compared to those with normal endothelial function.
Because NO has anti-inflammatory and anti-proliferative effects and therefore helps inhibit atherosclerosis, it is easy to see how endothelial dysfunction may contribute to future adverse cardiovascular events. Unfortunately the variability in such tests (e.g. due to time of day, food, menstrual cycle, temperature, etc.) means that no technique has yet been identified that would allow endothelial testing to attain routine clinical significance, although there are some tests under clinical evaluation such as measuring of arterial stiffness.
[edit] Testing
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.[2]
[edit] Prevention and treatment
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.[3] 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. Some studies have found antioxidants, potassium[4] and arginine supplementation to restore impaired endothelial function.
[edit] Epidemiology
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.[5]
[edit] See also
[edit] References
- ^ Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ (2005). "Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension". J Hypertens 23 (1): 7–17.
- ^ Endothelial dysfunction at 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.
- ^ Potassium softens vascular endothelium and increases nitric oxide release H. Oberleithnera,1,C. Calliesa,K. Kusche-Vihroga,H. Schillersa,V. Shahina,C. Riethmüllera,G. A. MacGregorb anH. E. de Wardenerb+ Author Affiliations aInstitute of Physiology II, University of Münster, D-48149 Münster, Germany; and bBlood Pressure Unit, Department of Cardiac and Vascular Medicine, St. George's University of London, London SW17 ORE, United Kingdom Communicated by Gerhard Giebisch, Yale University School of Medicine, New Haven, CT, December 21, 2008 (received for review August 20, 2008)
- ^ 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
