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Endothelial Dysfunction: A Common Factor in Diabetes, Atherosclerosis, and Hypertension

Jonathan Vellinga, MD -

Stroke Risk, Prevention, and the Atherosclerosis Connection

As a result of a reciprocal relationship, three widespread health conditions - diabetes, atherosclerosis, and hypertension all affect (and are affected by) a layer of cells that line our blood vessels called the endothelium. Addressing issues with the endothelium can help reduce the seriousness of these three health conditions and, in some cases, help prevent the conditions from forming. Likewise, managing or preventing diabetes, atherosclerosis, and hypertension can spare damage to blood vessels all over the body.

A large part of human suffering in the US is created by cardiometabolic diseases - diabetes, atherosclerosis, and hypertension, all of which can be a cause and an effect of damaged endothelium. By CDC estimates, an astounding 37 million Americans have diabetes, including about 8 million who have diabetes and don't know it (1). Atherosclerosis (the buildup of plaques in the arteries around the heart), also called "Coronary Artery Disease," affects about 18 million American adults (2). In 2020, over 670,000 deaths in the US were either primarily caused by hypertension or hypertension was a contributing factor (3). These statistics are sobering.

However, there is excellent news. Diagnosing and addressing endothelium issues has a massive, widespread positive impact on health. Not only does the treatment of endothelial problems reduce risks for severe illnesses, but it can also address the symptoms of concurrent diseases such as diabetes, atherosclerosis, and hypertension. Endothelial tissue treatments can stop feedback loops that result in a spiral of ever-decreasing health. Indeed, many of the treatments for diabetes, atherosclerosis, and hypertension aim to prevent or repair damage to the endothelium. This article examines the endothelium, how disruptions are diagnosed, and how it can be treated.

60,000 Miles of Endothelium in the Human Body?

The endothelium is a single layer of cells lining the inside surface of blood vessels in the vascular system, such as arteries, veins, and capillaries. Chemicals, toxins, stress, and medications can chemically interact with endothelium. The vascular endothelium (as opposed to the endothelium that lines the lymphatic system) has a lengthy list of functions, as it (4-6):

  • Lines about 60,000 miles of blood vessels in the human body

  • Helps blood reach all areas of the body

  • Controls the relaxation and contraction of blood vessels, allowing greater or lesser volumes of fluid to flow through the circulatory system

  • Forms "vascular tone" by affecting the contraction and relaxation of the vessels

  • Secretes growth promoters and inhibitors, affecting the growth of vessels

  • Regulates the movement of substances from the bloodstream into the tissues surrounding the vessels, relaxing when healing substances need to pass, but tightening to prevent toxic substances from passing into tissues

  • Produces nitric oxide (NO) and prostacyclin, which relax the vessels and help prevent blood clotting

  • Regulates coagulation of blood

  • Provides a space between human tissues and the blood where many significant interactions occur

  • Inflames as a result of remote factors, or produces inflammatory substances, such as Reactive Oxygen Species (ROS)

Nitric Oxide (NO) deserves special mention. Created by the endothelium, nitric oxide helps keep arteries open. Reduced NO can result in narrower blood vessels, which causes high blood pressure (hypertension). NO also fights inflammation, so if there is too little NO, inflammation in the artery walls can increase. Lack of NO can also increase the production of platelets, which are the elements in the blood that help create clots. Lastly, a lack of adequate NO can increase the porousness of blood vessel walls, allowing damaging substances through to nearby tissues (7).

It's evident that healthy endothelium and its tight control over NO is vital to many body functions. What happens when it goes awry?

Endothelial Dysfunction: When Artery Linings Fail

The endothelium performs delicate steps of accommodation, attempting to balance the relaxing, contracting, and inflammatory forces within the vessels it inhabits. Any strong disturbance of this sensitive mechanism can be called "endothelium dysfunction." Because vascular endothelium lines the blood vessels in so much of the body, imbalances tend to have widespread negative consequences, such as contributing to chronic health issues including atherosclerosis, diabetes, obesity, dyslipidemia (disordered cholesterol), and hypertension (8).

The details of how to classify different types of endothelial dysfunction are still being worked out, though one scientific review highlights three possible classifications (9). One classification is a distinction between acquired versus genetic. Risk factors can be passed down through family lines genetically. Or, endothelial dysfunction can be secondary to having some other disease (such as diabetes, hypertension, or atherosclerosis.) In secondary dysfunction, typically, the endothelium loses the ability to create nitric oxide (NO), which narrows blood vessels while at the same time increasing proinflammatory and pro-clotting factors.

Another classification centers on how much nitric oxide (NO) is produced in the endothelium. Lack of NO increases the risk of spasms and blood vessel blockage by a blood clot (called thrombosis). This mechanism ties into the dangers associated with diabetes, hypertension, dyslipidemia, atherosclerosis, and other health conditions. Too much NO, sometimes initiated by heart bypass surgery or sepsis, cascades into activating the immune system, creating free radicals, and releasing factors that increase clotting.

Symptoms of Endothelial Dysfunction: