Just like how roads shuttle vehicles throughout a city, blood vessels move blood throughout our body.  The inside of the blood vessels is coated by a single layer of flat cells called the endothelium.  But the endothelium does not just passively coat the insides of our blood vessels.  In fact, it performs many functions that are essential for our health.  

Source: Lifeline Cell Tech

A healthy endothelium is as thin as the thinnest human hair, yet it is critical for ensuring our blood remains a liquid. Liquid blood flows freely inside our endothelium-lined arteries, capillaries and veins, but as soon as it encounters anything that is not a healthy endothelial cell, say, a glass shard, a dirty nail, a sharp rock or anything else, a clotting reaction starts and it congeals into a solid mass. This makes perfect sense, since a blood clot is one of the first and quickest reactions to the damage caused by a wound, and it is needed to stop bleeding that could potentially lead to death.

But, if the endothelium is damaged from something other than an acute injury, blood can also clot inside blood vessels, causing big trouble. An unhealthy endothelium is one of the most prevalent causes of thrombosis, the technical name for blood clots that form inside the vessels and sometimes cause strokes, heart attacks and other issues. Fragments of solidified blood travel and can lodge inside small vessels, where they block oxygen flow, causing brain or heart cells to die. Smoking, uncontrolled high blood pressure, elevated levels of sugar in the blood (as seen in people with poorly controlled diabetes), unhealthy diets, and lack of physical activity are all conditions that can damage endothelial cells, increasing the risk of thrombosis.

There is a close link between blood clotting and inflammation, two processes are necessary to respond to potentially dangerous situations. When a rusty nail or an animal bite breaks the protective surface of the skin and causes bleeding, for example, blood clotting and inflammation act in concert to prevent you from losing too much blood, to help you fight infections, and to begin the process of healing. However, other threats can trigger blood clotting and inflammation even without causing visible damage to our bodily surfaces.

Several viruses, including SARS-CoV-2, the virus that causes COVID-19, can trigger inflammation even though they do not inflict visible wounds. However, because inflammation and blood clotting operate in tandem, the virus can also cause thrombosis.  As clots form inside blood vessels, they can travel to the heart and the brain, shutting them down just like they do during a heart attack or a stroke. Other organs may also fail, sometimes at the same time, spurring a potentially life-threatening situation. In fact, COVID-19 is more severe in individuals with preexisting conditions such as high blood pressure and diabetes because these ailments overtax the endothelium, priming it for an excessive response to the virus. The inflammation caused by the viral infection acts as the tipping point that precipitates thrombosis, which then damages the heart, brain and other organs.

A graphic showing SARS-CoV-2 causing a thrombosis to form. Source: American College of Cardiology.

Doctors treat severe cases of COVID-19 with medications that prevent blood clotting in an attempt to prevent or limit thrombosis. The most commonly used medication is heparin, a substance that limits blood clotting.

Heparin was discovered in 1916 by Jay McLean, who at the time was a second-year medical student at Johns Hopkins University. His mentor, William H. Howell, had charged McLean with the project of isolating a blood clotting molecule. While attempting to find such a molecule, McLean accidentally ended up discovering just the opposite— a compound that prevents blood clots. Howell recognized that such a molecule had its own value and called it heparin, from the Greek word for liver— the organ from which McLean first isolated it. The name stuck, and heparin is to this day one of the most effective tools against thrombosis.  It is imperative that heparin and other similar medications are administered with extreme precision because the margin between too much and too little blood clotting is very thin, with either of the two extremes leading to potentially catastrophic consequences. Administered at the right dose, heparin can prevent your body from creating thromboses in response to SARS-CoV-2 without causing excessive bleeding.

As important as the endothelium is in controlling blood clotting, this thinnest of biological carpets does so much more than that. Endothelial cells also make molecules that keep blood pressure under control by allowing vessels to relax, reducing resistance to the flow of blood. Endothelial cells also act as a barrier against the formation of fatty deposits called plaques that harden and narrow arteries, causing cardiovascular disease. But, again, only a healthy endothelium is able to properly perform these important functions.

Just like roads need regular maintenance, so does the endothelium. The best way to take care of our inner coating is to live a healthy lifestyle by avoiding smoking, eating healthy foods, and being physically active, while keeping blood pressure and sugars under control.  By taking these measures, we can help ensure that the inner surface of our body’s roadway is ready for even the heaviest city traffic.  


  • Giamila Fantuzzi

    Giamila Fantuzzi is a Professor in the Department of Kinesiology and Nutrition at the University of Illinois at Chicago, where she teaches and studies cytokines and inflammation. She is the author of Body Messages: The Quest for the Proteins of Cellular Communication (Harvard University Press).

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