General Health

Endothelial Dysfunction: Causes, Symptoms & Treatments

Endothelial dysfunction is a growing concern. This is a condition that affects the endothelial layer. The layer is found in blood vessels. Lymphatic vessels also contain endothelial cells.

The layer plays a crucial role in ensuring blood flow is regulated properly. When dysfunction occurs with the layer, there are several complications a patient may experience. 

We take a look at what the endothelial layer is. We will also consider its function and what causes endothelial dysfunction. This post also considers how endothelial dysfunction is diagnosed. We will also look at the treatment options currently available for this condition. 

Function Of The Endothelial Layer

Before looking at what endothelial dysfunction is, understanding the function of this layer is important. Endothelial function affects the blood vessels and the entire cardiovascular system. This layer consists of squamous endothelial cells.

Blood carries oxygen and nutrients to every part of the body. This makes blood a critical element of life.

Cardiovascular disorders are major killers among the general population. The World Health Organization1 reports that about 31% of all global deaths are related to heart disease. These conditions claim about 17.9 million lives each year. 

The layer is also sometimes referred to as the endothelium. It is a single layer that is located on the inner wall of blood vessels and arteries. The endothelium layer also lines the lymphatic vessels. These vessels are part of the lymphatic system, which helps in regulating the body’s immune responses. 

The endothelial cells that form part of this layer have multiple roles to play in the cardiovascular system. The endothelium is a continuous layer that is found in blood vessels throughout the body2.

Studies have revealed that these cells outline blood vessels in the brain, heart, muscle tissue, lung, and skins. Capillaries and arteries also contain an endothelial layer. 

One of the most important functions provided by the endothelial layer is to assist in the regulation of blood vessel dilation. The layer helps to dilate blood vessels. When blood vessels dilate, they allow more blood to flow through.

The layer also ensures blood vessels can constrict. This helps to reduce the risk of too much blood flowing to certain parts of the body. Reactive hyperemia is just one potential concern in such a scenario.

Blood vessel dilation and constriction are not the only functions of the endothelial layer. Other functions performed by these cells include:

  • The endothelial layer has a tone that contributes to the control of blood pressure

  • The tone of the endothelial layer also determines how much work is needed from the heart to pump blood through the body. 

  • The layer assists in the regulation of mechanisms involved in blood clotting. 

  • Endothelium cells help to control toxic substances in the blood. They help to reduce the number of toxic substances that tissues in the body are exposed to. 

  • Inflammation in tissues throughout the body is also regulated by the endothelial cells in blood vessels. 

  • This layer assists in regulating the transference of fluids, as well as electrolytes. This helps to ensure enough fluids are released into tissues. Excess fluids can also be removed through the help of the endothelial layer. 

For the body to function properly, a healthy endothelial layer is critical. It ensures blood is delivered to all tissues – and helps to reduce toxin exposure of organs and tissues. 

What Is Endothelial Dysfunction?

Endothelial dysfunction is a condition that refers to problems with the endothelial layer in blood vessels. Endothelial activation essentially fails too. In some studies, the prevalence of endothelial dysfunction was found to be as high as 58%3.

There are some conditions that seem to greatly increase a patient’s risk of developing this condition. Endothelial dysfunction is also linked to several complications. 

When this condition develops, the endothelial cells fail to perform the functions they are supposed to do. It can affect the brachial artery, a coronary artery, and all other blood vessels in the body. This can lead to quite a large number of problems.

Issues can develop with all functions that are associated with endothelial dysfunction. Blood vessel constriction and dilation become problematic, for example. Different types of the condition exist. Microvascular dysfunction is another example. 

Tissues that rely on adequate blood supply can suffer in the process. This is especially the case when vascular endothelial dysfunction causes poor blood flow to certain areas of the body. It can also lead to arterial stiffness. In turn, problems with endothelial progenitor cells can develop. These factors can adversely affect vascular function. 

It is possible to treat endothelial dysfunction. Long-term treatment is needed, however. There is various treatment available. A patient will often be advised to make certain lifestyle changes. This may help to improve endothelial function. Accompanying conditions also need to be treated to avoid further damaging arteries and blood vessels. 

Studies have revealed that the condition is more common in women compared to men. 

Symptoms Of Endothelial Dysfunction

It is often difficult to provide an accurate overview of symptoms associated with the condition. This is because people will often not experience obvious symptoms when the condition is still in its early stages.

As endothelial dysfunction progress, it tends to cause complications to develop. These complications can cause the patient to experience symptoms. 

  • Chest pain is one of the most common symptoms that a patient experiences when they have endothelial dysfunction4. This is also referred to as angina. When the patient suffers from emotional stress, chest pain will likely become worse. The chest pain is also worse when the patient participates in physical activity. 

  • Angina occurs due to a narrowing of the blood vessels. There may be a significant constriction in arteries close to the heart. In turn, this causes pain symptoms to develop in the area. 

  • In women, there may also be an increase in the intensity of chest pain during a menstrual period. 

  • Shortness of breath sometimes happens in people with endothelial dysfunction. This is not a symptom that everyone with the condition will experience. 

These are the main symptoms generally linked to endothelial dysfunction. When other symptoms occur, too, they will usually be caused by complications. 

It is also important to note that endothelial dysfunction is sometimes considered to be a preceding condition of atherosclerosis5. This means a patient with the condition may go on to develop atherosclerosis. The risk is significantly increased when no treatment is provided to the patient. 

Causes Of Endothelial Dysfunction

Understanding the causes of endothelial dysfunction can help a person realize their own risk of the disease. It also helps a person understand why they might have developed the condition.

In many cases, a doctor will also try to determine the potential cause behind the condition. This may help the doctor when developing a treatment plan. 

Research is still being done to determine all of the potential causes related to endothelial dysfunction. It is known that low Nitric Oxide levels in the walls of blood vessels may contribute to the condition. 

Nitric oxide is a type of gas in the body. It travels through the blood circulatory system. L-arginine, an amino acid, is metabolized and converted into nitric oxide. The gas has a short half-life. It has a local action within blood vessels.

The gas helps to regulate the tone of blood vessels. It also contributes to certain functions of the endothelial cells in blood vessels and arteries. Asymmetric dimethylarginine is another compound that contributes to nitric oxide production.

When nitric oxide levels are low, blood vessels tend to constrict more than usual. Platelet activation also occurs. This may lead to excessive blood clotting. Nitric oxide deficiency is also known to have a pro-inflammatory effect on the walls of blood vessels. All of these side-effects related to a deficiency in nitric oxide can cause problems with the endothelial layer. 

It is important to note that low nitric oxide levels may not be the only cause of the condition. Studies have found that the endothelial cells in blood vessels are highly suspectable to oxidative damage. With this in mind, failure to provide adequate antioxidants to the body may increase the risk of endothelial dysfunction.

Antioxidants are responsible for warding off oxidative stress. It is a relatively common issue with reactive oxygen species in the body. If there are not enough antioxidants present, then the blood vessel walls may suffer damage. This can lead to problems with the endothelial cells. 

With this in mind, it means that a deficiency in certain nutrients might also be a contributing factor to endothelial dysfunction. Vitamin C, for example, is a potent antioxidant. It is known that this vitamin helps to reduce oxidative stress in the body. It fights against free radicals. Low consumption of vitamin C may also interfere with the regulation of nitric oxide5. 

Disorders And Habits Associated With Endothelial Dysfunction

We understand that a lack of nitric oxide may be a leading cause of endothelial dysfunction. Unfortunately, it is difficult for a person to tell if they have enough nitric oxide in their body.

Researchers are still looking to discover more accurate data on the pathways of the condition. 

It has been found that some conditions and habits seem to be linked to endothelial dysfunction. Researchers found that people with certain habits are more likely to develop dysfunction in their endothelial layer. Additionally, it was also found that those who have been diagnosed with certain conditions also seem to be more likely to develop this disease. 

  • Aging is one of the factors that contribute to an increased risk of endothelial dysfunction. Genetics also seems to play a role. There does seem to be a higher risk in people with a family history of this condition and other cardiovascular events

  • There are two crucial habits that patients need to take note of. Both of these habits have been linked to a higher risk of endothelial dysfunction. They include smoking, as well as a sedentary lifestyle. 

  • One study found that about 60% of senior citizens do not get enough exercise6. The same study claims that some reports have found up to 67% of the worldwide population may not get enough physical activity.

  • A sedentary lifestyle increases the risk of heart disease and other cardiovascular disorders. Combine this with old age, and the patient has a much greater risk of developing endothelial dysfunction. 

There are a few conditions that have also been found to have a link to endothelial and microvascular endothelial dysfunction. These conditions include:

  • Hypertension, which is one of the major cardiovascular risk factors. Hypertensive patients also face other risks related to their heart health.

  • High LDL cholesterol levels can affect coronary endothelial function. With this in mind, it may be a risk factor for coronary endothelial dysfunction too. 

  • High triglyceride levels.

  • Type 2 Diabetes and insulin resistance.

  • Heart failure.

  • Osteoporosis.

  • Hypothyroidism.

People who frequently suffer from infections may also be more likely to develop endothelial dysfunction. This is rather common in diabetic patients. Additionally, there is some evidence that shows emotional stress may be another factor involved in the development of this condition.

Other factors, like NADPH oxidase, need to be considered. Some factors lead to specific problems, such as coronary microvascular dysfunction, which only affects certain arteries.

Patients who obtain radiation therapy and chemotherapy for cancer may also experience problems with their endothelial cells. These treatments may cause damage to blood vessel walls. In turn, endothelial dysfunction can occur. 

Possible Complication Of Endothelial Dysfunction

Endothelial cells have a lot of functions to perform in the cardiovascular system. Due to these functions, the development of impaired endothelial function can cause several complications.

Existing cardiovascular conditions can also become worse when the patient develops endothelial dysfunction. 

The primary issue with endothelial dysfunction is vascular complications. It is especially the case with vascular endothelium problems. This layer in the blood vessel wall help with vasodilation and the constriction of arteries.

When these functions do not work, too much or too little blood may be pumped through arteries. There may be an increase in pressure too, which can cause damage to the walls of these blood vessels. 

Patients with endothelial dysfunction can develop vascular disease as a complication. This includes atherosclerosis. In such a case, blood flow can be adversely affected. There is also an association between endothelial dysfunction and metabolic disorders7. 

Researchers also note that endothelial dysfunction may be an early sign of coronary artery disease. The dysfunction in the endothelial layer reduces the protective functions of the blood vessel wall. 

Furthermore, it has been found that coronary circulation alterations can occur in patients with endothelial dysfunction that affect peripheral arteries

Endothelial apoptosis needs to be considered too. In this scenario, the lack of nitric oxide synthase in the body leads to more serious problems. The patient’s endothelial cells may die off. This further increases the risk of impaired endothelial function.

The patient also gets a higher risk of heart disease. This means there is a greater likeliness that the patient may later suffer from myocardial infarction and issues with the porcine coronary arteries. 

Diagnosis

The process of diagnosing endothelial dysfunction starts with a consultation. A doctor needs to ask the patient about the symptoms they experience.

The doctor also needs to review the patient’s medical history. Patients who have a history of heart diseases may be more suspectable to endothelial dysfunction. The doctor may also ask about a family history of heart disease. 

In many cases, the patient will not need to undergo specific tests for the diagnosis of endothelial dysfunction. Doctors will generally assume endothelial dysfunction in patients with associated conditions. Examples include patients with hypertension.

Coronary artery disease is also known to be associated with endothelial dysfunction. Patients with significant risks associated with heart disease may also be assumed to have endothelial dysfunction if they suffer from chest pain and related symptoms. Cardiovascular risk factors are taken into consideration.

There are scenarios where a doctor will order certain tests. This is usually the case when there is no explanation for endothelial dysfunction symptoms. The patient may have these symptoms but have no existing heart disease. There might also be no family history of heart disease. Tests are also requested if the doctor suspects the patient may suffer from cardiac syndrome x. 

Catheterization may be used for testing purposes. In some cases, a test is performed using ultrasound instead. Acetylcholine is administered to the patient during the test. The test itself will provide details on the dilation of blood vessels. 

The doctor will be able to see if blood vessels are able to dilate properly. If there are problems with the dilation process, it may be linked to a dysfunction of the endothelial layer. 

Other tests are generally not required to confirm a diagnosis for endothelial dysfunction. It should be noted that sometimes additional tests will be requested. This is the case when the doctor expects other causes behind the symptoms that the patient complains about. The doctor needs to rule out problems like heart failure and atherosclerosis. 

Treatments

During the earlier stages, endothelial dysfunction is sometimes considered a reversible condition. When the patient does not implement appropriate treatments early on, it may lead to long-term complications. 

There are risk control methods that doctors will often use as a way of treating endothelial dysfunction. Patients are also advised to make important lifestyle changes.

Several habits may contribute to problems with the endothelial cells in blood vessels. By addressing these habits, further damage to these cells can be reduced. Some lifestyle changes could also help to improve the condition of endothelial cells. In such a case, risks associated with the disease may be reduced. 

Lifestyle Changes

If the patient does not have any severe heart diseases with endothelial dysfunction, they may want to try a few lifestyle changes first. There are a few ways to improve the condition by simply making a few changes to the individual’s lifestyle. 

There is some evidence that the Mediterranean diet may be useful for patients with endothelial dysfunction. This diet reduces the intake of processed foods. It also reduces the intake of foods that are high in fats and other compounds generally considered harmful to the body. 

Patients who do not wish to implement a Mediterranean diet can consider making other dietary changes. They can start to add more olive oil to their food – and avoid using other types of oils. Olive oil is rich in fatty acids and has been shown to produce anti-inflammatory effects in the body. 

The person should also consider drinking green tea regularly. There are anti-inflammatory agents in green tea. This tea is also high in antioxidants. We already mentioned the important role that antioxidants play in helping to fight against endothelial dysfunction. 

In addition to dietary changes, making more ties to exercise is important too. Aerobic exercise is critical for people with endothelial dysfunction. 

Losing Weight

Obesity and being overweight increases the risk of diabetes and heart disease. These form part of a collective range of conditions called metabolic disorders. The risk of blood vessel damage increases with weight. 

These factors can all contribute to endothelial dysfunction. 

Losing weight is another effective strategy to help reduce the complications associated with endothelial dysfunction. 

There are several strategies that can help a person lose weight. Implementing an exercise plan and an appropriate diet program is helpful. A caloric deficit will be necessary. If the patient adopts a Mediterranean diet as previously recommended, it already provides them an advantage. 

Medical Treatments

There are no specific drugs made to treat endothelial dysfunction. A few pharmaceutical drugs have, however, been found to provide helpful effects in patients with this condition. 

Statin drugs are sometimes prescribed for patients with endothelial dysfunction. In some cases, a doctor may also provide the patient with an ACE inhibitor

Recent studies also show that other drugs might be helpful too. L-arginine may help to address a deficiency of nitric oxide, for example.

Patients are also being provided with sildenafil to help boost nitric oxide in their blood vessels. When nitric oxide deficiency is addressed, it also helps to prevent further problems with the endothelial layer. 

Other drugs that are also being used as treatments for endothelial dysfunction recently include:

  • Aspirin

  • Ranolazine

  • Nifedipine

In female patients, estrogen may sometimes be used as a treatment. The use of estrogen as part of hormone replacement therapy has shown potential when used in women with endothelial dysfunction. 

Conclusion

The endothelial cells that are found in the walls of blood vessels can become dysfunctional. When this happens, a patient is at risk of certain complications. Recognizing the condition early on is essential. This can help to provide the patient with a more effective treatment strategy.

Treatment helps to reduce the risk of complications associated with endothelial dysfunction. There are various treatments available. A doctor first needs to assess the severity of the condition before determining the best treatment to use. 

Sources

  1. World Health Organization. Cardiovascular Diseases. [online] Available at: https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1
  2. The Endothelium. (2011) Chapter 2: Multiple Functions of the Endothelial Cells. [online] Available at: https://www.ncbi.nlm.nih.gov/books/NBK57148/
  3. Clinical Cardiology. (2010) The Prevalence of Endothelial Dysfunction in Patients With and Without Coronary Artery Disease. [online] Available at: https://pubmed.ncbi.nlm.nih.gov/21184558/
  4.  Stanford Health Care. Endothelial Dysfunction. [online] Available at: https://stanfordhealthcare.org/medical-conditions/blood-heart-circulation/endothelial-dysfunction/symptoms.html
  5.  Oregon State University. Endothelial Dysfunction. [online] Available at: https://lpi.oregonstate.edu/mic/health-disease/endothelial-dysfunction
  6.  International Journal of Environmental Research and Public Health. (2013) Prevalence of Sedentary Behavior in Older Adults: A Systematic Review. [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881132/
  7.  ScienceDirect. (2017) Endothelial Dysfunction. [online] Available at: https://www.sciencedirect.com/topics/medicine-and-dentistry/endothelial-dysfunction

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