Endothelial Dysfunction: When Blood Vessels Turn Bad
Think of your blood vessels like a garden hose. While not the same size, a hose and an artery both share some common characteristics — they’re conduits for moving fluid, the transmit their contents in one direction (usually), and they both have a little bit of elasticity that allows them to buffer the pressure inside and expand a little without breaking.
Our blood vessels (arteries and veins) are pretty amazing. We have several types of vessels including large elastic arteries such as the aorta, conduit arteries like the brachial and femoral arteries, medium-sized muscular arteries which are surrounded by smooth muscle, and smaller arterioles and capillaries that distribute blood to our muscles, organs, and tissues.
Our fine-tuned vascular system serves several purposes — delivering blood/nutrients/oxygen and regulating blood pressure are two critical ones.
In order to properly regulate blood pressure and increase blood flow in response to things like exercise, our blood vessels need to maintain a fine balance between contraction and relaxation; also known as vasodilation and vasoconstriction. In general, vasodilation leads to a decrease in blood pressure and an increase in blood flow through an artery, while vasoconstriction does the opposite — increasing blood pressure and restricting blood flow.
How does the vessel know which action is required? Since our vascular system is under involuntary control (you can’t just “think” your way to vasodilation), several internal mechanisms and sensors are in place that cause signals for contraction or relaxation of blood vessels.
For instance, when blood flow increases through an artery (at the start of exercise, for instance), the shear force of blood on the lining of the vessel wall (known as the endothelium) causes an increase in a molecule known as nitric oxide — or NO for short. NO can then diffuse through the thin vessel layer into the smooth muscle, where it causes a cascade of events that end in vascular relaxation and vasodilation. Including NO, the molecules that cause vasodilation are termed (endothelium-derived relaxing factors; EDRFs).
NO protects the vascular system against “insults” like blood clotting or formation of atherosclerosis. Interestingly, when blood starts to clot in a vessel, the clot releases molecules that actually serve as a signal for NO production to occur. This is sort of a “feedback” mechanism to prevent clot formation.
On the other hand, vasoconstriction can also be caused by several molecules. Reactive oxygen species, high blood glucose, hypoxia (low oxygen), and increased sympathetic nervous system activity can all activate signal cascades that lead to smooth muscle contraction. The factors that lead to vasoconstriction are colloquially termed “endothelium-derived contracting factors; EDCFs).
A balance of EDRFs and EDCFs is necessary to fine-tune vascular tone as our body sees fit. Too little tone, and we’d faint due to a lack of blood pressure. Too much tone, and high blood pressure (hypertension) can ensue.
It is precisely this imbalance that is the cause of so many cardiovascular dysfunctions. When the body becomes less adept at producing and/or responding to NO and gains the propensity to produce more contracting factors, this is termed endothelial dysfunction.
Back to our hose analogy, except now imagine a PVC pipe. While the stiffness and material may not be illustrative, the concept is that now when you have an increase in flow, you’ll no longer get the “expansion” that you would with a more flexible, elastic hose.
Endothelial dysfunction is a risk factor for developing cardiovascular disease and atherosclerosis. A dysfunctional endothelium means that the blood vessels are less protected from plaque formation, have a higher tone (and pressure), and begin to produce toxic reactive oxygen species rather than beneficial NO.
In addition to being a risk factor, several diseases/conditions actually cause endothelial dysfunction. Obesity and diabetes, for instance, can lead to endothelial dysfunction through high blood glucose or insulin resistance. High glucose (hyperglycemia) directly causes endothelial dysfunction by reacting with protein inside the blood vessel wall.
Endothelial function can also be improved. Interventions like exercise training are a potent stimulus for the vessels to adapt to producing more NO and responding more profoundly to it. In fact, exercise training can reverse endothelial dysfunction resulting from aging or diabetes/obesity.
The blood vessels are a pretty “plastic” (in this case meaning adaptable) organ. They respond intensely both to heavy use and heavy disuse, and adapt to the stimulus that is imposed on them.
Even more interesting may be the fact that your endothelial function is a pretty good predictor of health. We know of the “traditional” cardiovascular risk factors like age, gender, smoking status, blood pressure, body fat, diabetes, etc. However, endothelial function can independently predict your risk of having a cardiovascular event or death. Whether assessed in the coronary vessels (in the heart) or brachial artery, better vascular function is associated with a lower risk of death and disease.
The health of your arteries might be one of the most potent predictors of your overall disease risk. It’s an aspect that is sometimes neglected in favor of easier to measure outcomes like blood glucose, body fat, or cholesterol. But I think a measure of actual function vs. some biomarker serves a larger purpose in terms of assessing overall wellness. Not that biomarkers are unimportant, but a “functional biomarker” can actually correlate to how well you respond to a stimulus — it’s a measure of performance. Functional biomarkers are often influenced by a suite of individual molecular biomarkers. Vascular function is just one example — it probably measures the interaction among multiple molecular and cellular regulators, rather than just one or two. In this case, it provides a superior snapshot to a blood draw taken at a single time point.
Our vascular endothelium contains over a trillion cells, weighs about 1 kilogram, and covers a surface area of about 3 square meters in the human body. This intricate system exerts profound influence over our health, which is why prioritizing cardiovascular wellness can undoubtedly influence how well, and perhaps how long you live.
References
Widmer RJ, Lerman A. Endothelial dysfunction and cardiovascular disease. Glob Cardiol Sci Pract. 2014;2014(3):291–308.
Ras RT, Streppel MT, Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int J Cardiol. 2013;168(1):344–51.
Radenković M, Stojanović M, Janković R, Topalović M, Stojiljković M. Combined contribution of endothelial relaxing autacoides in the rat femoral artery response to CPCA: an adenosine A2 receptor agonist. ScientificWorldJournal. 2012;2012:143818.
