Endothelial dysfunction

# Overview
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.)

# Pathophysiology
The surface are of endothelial cells in the body is as large as a tennis court. There are a trillion endothelial cells in the body.
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.
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. 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. 

# Acetylcholine
Normal arteries vasodilate in response to acetylcholine, atherosclerotic arteries constrict.  Endotheilial function in response to exercise and mental stress is a measure endothelial health.  This effect is mediated by abnormalities in the endothelial cells.  Vasodilation is dependent upon the release of nitric oxide by healthy endothelium.
Endothelial dysfunction:
- Cannot be detected on a non-invasive test.
- Is related to diastolic dyfunction
- Related to future risk of stroke and TIA
- Is related to vulnerable plaque and a necrotic core and a higher risk of plaque rupture
- Is related to LpLA2, but not CRP
- Is associated with reductions in endothelial progenitor cells with impaired response to injury
- Is a systemic disorder (TIA /stroke sleep apnea, ED)

# Reactive Hyperemia
Forearm reactive hyperemia after a blood pressure cuff is let down is a test of endothelial function.  There should be vasodilation after the cuff is let down.  An abnormal response predicts future coronary and peripheral events.

# Treatment
- Lipid-lowering
- Exercise
- ACE inhibition
- Calcium channel blockers
- L-arginine

# NO