Endothelial Dysfunction

Arteries. Science Photo Library - PASIEKA/Getty Images

Endothelial dysfunction is a condition in which the endothelium (inner lining) of blood vessels fails to function normally. In recent years it has become apparent that endothelial dysfunction is an important factor in coronary artery disease (CAD), hypertension, microvascular angina (cardiac syndrome x), diastolic dysfunction, and other cardiovascular conditions.

What Does The Endothelial Layer Do?

In arteries, the endothelial layer of cells has several very important functions.

These include maintaining the proper dilation and constriction of the blood vessels (that is, maintaining vascular tone), regulating blood clotting and inflammation, controlling the volume of fluid and the amount of electrolytes and other substances that pass from the blood into the tissues, and protecting the tissues from toxic substances. The proper functioning of the endothelium is necessary for the normal function of the body’s tissues and organs.

When endothelial dysfunction is present, the ability to perform one or more of these functions is reduced.

What Is The Mechanism Of Endothelial Dysfunction?

Researchers are working hard to understand all the causes of endothelial dysfunction. At this point it is apparent that endothelial dysfunction is related to abnormally reduced levels of nitric oxide (NO) in blood vessel walls.

NO is a gas that is produced by metabolism of an amino acid (L-arginine).

NO, which has a very short half life, acts locally within blood vessels to help modulate vascular tone and other vital endothelial duties. A deficiency in NO production leads to excess constriction of blood vessels (which can produce hypertension), contributes to the activation of platelets (leading to blood clotting), and increases the stimulation of inflammation in blood vessel walls and the permeability of the vessel walls to damaging lipoproteins.

To summarize, endothelial dysfunction is characterized by reduced vascular NO levels, which, in turn, leads to several abnormalities in blood vessel function that tend to promote atherosclerosis. In addition, endothelial dysfunction can directly cause abnormal constriction of the small arteries, and is thought to be a major factor in producing cardiac syndrome x and potentially, diastolic dysfunction.

What Causes A Person To Develop Endothelial Dysfunction?

The precise pathways by which a person develops endothelial dysfunction are still being worked out. It seems clear that numerous factors contribute to it, including:

How Is Endothelial Dysfunction Diagnosed?

Making a formal diagnosis of endothelial dysfunction is usually not necessary.

Some degree of endothelial dysfunction can be safely assumed in anyone who has CAD, hypertension, or major risk factors for heart disease (especially those listed above).

So actually measuring a patient's endothelial function is not routinely done. But if endothelial dysfunction is suspected in a person without clear reasons for it (such as a person thought to have cardiac syndrome x), a diagnosis can be confirmed by tests that measure the ability of the blood vessels to dilate and/or constrict in response to drug administration.

How Is Endothelial Dysfunction Treated?

Endothelial function can be improved by the measures that are commonly urged to reduce the risk of CAD, including weight loss, exercise, smoking cessation, control of hypertension, and control of diabetes.

Certain of these risk control measures have been well documented to reduce endothelial dysfunction. These include:

In addition, several medications are being studied specifically to see whether they can improve endothelial dysfunction in a clinically meaningful way. Some of the agents that appear to show promise include nifedipine, some ACE inhibitors, estrogen, ranolazine, and sildenafil.


In recent years medical researchers have identified endothelial dysfunction as an important underlying cause of many cardiovascular problems. While there is already a lot we can do to reduce endothelial dysfunction, research is underway to develop new ways of preventing and treating it.


Crea F, Camici PG, Bairey Merz CN. Coronary microvascular dysfunction: an update. Eur Heart J 2014; 35:1101.

Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2010; 56:e50.

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