Endothelial dysfunction
Encyclopedia
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. 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.
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.
(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.
(commonly found in hydrogenated products such as margarine
) and the development of endothelial dysfunction. 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
and arginine
supplementation to restore impaired endothelial function.
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
(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. Normal functions of endothelial cells include mediation of coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
, platelet adhesion, immune function and control of volume
Volume
Volume is the quantity of three-dimensional space enclosed by some closed boundary, for example, the space that a substance or shape occupies or contains....
and electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
content of the intravascular and extravascular spaces. Endothelial dysfunction can result from and/or contribute to several disease processes, as occurs in septic shock
Septic shock
Septic shock is a medical emergency caused by decreased tissue perfusion and oxygen delivery as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome and death...
, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, hypercholesterolaemia, diabetes, it can also result from environmental factors, such as from smoking tobacco products and exposure to air pollution.
Atherosclerosis
Endothelial dysfunction is thought to be a key event in the development of atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
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
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
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.
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 oxideNitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
(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
Iontophoresis
Iontophoresis is a technique using a small electric charge to deliver a medicine or other chemical through the skin. It is basically an injection without the needle...
of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
, 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
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
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
Angiogram
Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins and the heart chambers...
. 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
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
. 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.
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.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 fatTrans fat
Trans fat is the common name for unsaturated fat with trans-isomer fatty acid. Because the term refers to the configuration of a double carbon-carbon bond, trans fats are sometimes monounsaturated or polyunsaturated, but never saturated....
(commonly found in hydrogenated products such as margarine
Margarine
Margarine , as a generic term, can indicate any of a wide range of butter substitutes, typically composed of vegetable oils. In many parts of the world, the market share of margarine and spreads has overtaken that of butter...
) and the development of endothelial dysfunction. Other factors have been identified as improving endothelial function and include cessation of smoking, loss of weight and treatment of hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and hypercholesterolemia
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
amongst other things. Some studies have found antioxidants, potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
and arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
supplementation to restore impaired endothelial function.