The Glycocalyx: A Little Known Connection with Heart Disease, Diabetes, Coronavirus, Digestion and Immune Health
Hello, I am Julie and I am a clinical nutritionist with functional medicine training. I specialize in restoring balance in complex, chronic and acute health conditions. I welcome you to peruse other articles that may be of interest to you in your health investigation!
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The glycocalyx is a little known structure in the body, rarely discussed in holistic health circles. In this article, I will deliver information about how it impacts numerous critical functions in the body, from cardiovascular health to diabetes, digestion, and immune regulation.
What is the Glycocalyx?
The glycocalyx is a thick coating around certain cells in the body that assists them in withstanding constant pressure. Made of sugars, proteins & glycolipids, the glycocalyx is found in endothelial cells (lining of blood vessels), bacteria (including healthy gut bacteria), and in the microvilli of the small intestines. The body uses the glycocalyx as an identifier to distinguish between its own healthy cells, transplanted tissues, diseased cells and invading organisms.
In the gut, the glycocalyx has enzymes that support digestion and absorption. It also acts as a protective barrier, preventing debris from entering the system inappropriately.
In the microvascular tissue, the glycocalyx serves as a vascular permeability barrier by inhibiting coagulation and leukocyte adhesion. It also prevents cholesterol from adhering to the walls of the vessels. Coagulation presents a risk for thrombrosis (clotting) in the blood vessels. Cardiovascular health is also dependent upon proper volume and flow in our blood vessels which may be impeded by cholesterol adhesion. With regards to the immune system, if leukocytes are adhering to blood vessel walls, they are no longer free to travel and complete their tasks in the immune system.
Additionally, in the blood vessels, the glycocalyx allows nitric oxide to be released through shear stress-induction as the blood flows through the vessels. A healthy glycocalyx also provides the defense mechanism (superoxide dismutase, or SOD) against the leaking of superoxide which can react with nitric oxide and create peroxynitrite, a very potent and damaging oxidant. The importance of nitric oxide cannot be minimized - a full discourse on this topic can be found here.
Lastly, in the microvascular tissue, the glyocalyx affects filtration of fluid from the capillaries into interstitial fluid, which makes up the majority of the extracellular fluid (ECF). ECF provides the medium for the exchange of substances between itself and the body’s cells. This can take place through dissolving, mixing and transporting in the fluid medium. Substances in the ECF include dissolved gases, nutrients, and electrolytes, all of which are needed to maintain life. A small portion of the ECF is the lymph fluid, necessary for cleansing the blood and fighting infection. Other miscellaneous functions of the glycocalyx are:
Cushions plasma membrane and protects it from chemical toxicity
Enables immune system to selectively attack/destroy pathogens and protect self tissue (a major factor in preventing autoimmune disease)
Forms compatibility for transplants and transfusions
Regulates inflammation in the endothelium
Helps sperm to recognize and bind to eggs
Supports embryonic development
Mediates onset of alveolar microvascular dysfunction in Acute Respiratory Distress Syndrome (ARDS)
Fascinating Connections with Heart Disease and Microbrial Tissue in the Vessels
In a scientific review of atherosclerotic patients completed by Ravsnkov and McCully (1), the following statements clarify that the typical associations with cholesterol and morbidity are unfounded:
1. The concept that high LDL cholesterol causes endothelial dysfunction is unlikely because there is no association between the concentration of LDL cholesterol in the blood and the degree of endothelial dysfunction.
2. The concept that endothelial damage leads to influx of LDL cholesterol is unlikely as well, because the atheroscloertic plaques seen in extreme hyperhomocysteinemia caused by inborn errors of methionine metabolism do not contain any lipids in spite of pronounced endothelial damage.
3. No study of unselected individuals has found an association between the concentration of LDL or total cholesterol in the blood and the degree of atherosclerosis at autopsy.
4. In studies of women and the elderly, hypercholesterolemia is a weak risk factor for cardiovascular disease, or in most cases, not a risk factor at all.
So, what is causing the blockage and CV dysfunction? The authors of this review state “Little attention has been paid to the formation of lipoproteins as part of a nonspecific immune defense system that binds and inactivates microbes and their toxins effectively by complex formations. Because of high extra-capillary tissue pressure, aggregates of such complexes may be trapped in vasa vasorum of the major arteries. This complex formation and aggregation may be enhanced by hyperhomocysteinemia.”
They further state “The content of necrotic debris and leukocytes and the higher temperature than its surroundings give the vulnerable plaque some characteristics of a micro-abscess that by rupturing may initiate an occluding thrombosis. This suggested chain of events explains why many of the clinical symptoms and laboratory findings in acute myocardial infarction are similar to those seen in infectious diseases. It explains the presence of microorganisms in atherosclerotic plaques and why bacteriemia and sepsis are often seen in myocardial infarction complicated with cardiogenic shock. It explains the many associations between infections and cardiovascular disease. And it explains why cholesterol accumulates in the arterial wall. Some risk factors may not cause vascular disease directly, but they may impair the immune system, promote microbial growth, or cause hyperhomocysteinemia, leading to vulnerable plaques.” Essentially, the understanding is that microbial presence in the vessel walls is damaging the endothelium and the glycocalyx, and causing an aggregation of cholesterol particles which are adhering to vessel walls. Microbes identified in 50% of plaque samples include spirochetes, chlamydia, herpes and cytomegalovirus (CMV). This is critical information for understanding the intersections between cardiovascular disease and immune dysfunction. It is also critical information for understanding what a huge role the glycocalyx plays in resolution of these problems.
A century ago, bacteria and viruses were considered as the main causes of atherosclerosis, a view that was based mainly on post-mortem observations. Ravnskov & McCully are giving new areas of support to this age-old consideration. Evidence has been reported more recently, suggesting that infectious processes may play a role in cardiovascular disease:
Cardiovascular mortality increases during influenza epidemics
A third of patients with acute myocardial infarction or stroke have had an infectious disease immediately before onset
Bacteriemia and periodontal infections are associated with an increased risk of cardiovascular disease
Serological markers of infection are often elevated in patients with cardiovascular disease and are also risk factors for such diseases
A role of infectious agents is suggested by the narrowing of the coronary arteries seen in children who died from an infectious disease
With a healthy immune system, the microorganisms may be eliminated, new capillaries will enter the lesion, and reparative processes will convert the dead tissue into a stable, fibrous plaque. But in the case of an insufficient clearing of the microorganisms and the ensuing inflammatory response, cell death may accelerate and impede repair processes, creating a vulnerable plaque which in turn creates a preferential site for occluding thrombi. While attack and inflammation are natural to the body’s immune response, if they are not successfully completed and result in resolution, there is lingering dysfunction, inflammation and possible necrosis of tissue.
Dr. Axel Haverich, MD has proposed that “atherosclerosis represents a microvascular disease rather than a large vessel disease…Large arteries are involved secondarily after microvascular disease of the vessel wall.” He also states that endothelium dysfunction is the primary target when looking at other proposed theories of atherosclerosis involving responses to trauma and inflammation.
SARS CoV-2 and the Glycocalyx
In their peer-reviewed paper, authors Okada, Yoshida, Hara, Ogura and Tomita make the connections between thrombosis, mortality risk, and SARS CoV-2. The authors state: “Endothelial dysfunction unbalances the vascular equilibrium to favor vasoconstriction, with subsequent organ ischemia, inflammation with associated tissue edema, a pro‐coagulant state, and is a major determinant of microvascular dysfunction. The capillary, which is also referred to as a microvascular endothelial cell, has a diameter of 5‐20 µm. The exchange of various molecules, including oxygen, between the blood and organs only occurs via the capillaries. Accordingly, the capillaries play a central role in systemic microcirculation. We propose that thrombosis may be associated directly with both the onset and exacerbation of COVID-19 (e.g., ARDS, heart failure, cerebral infarction) via the endothelial glycocalyx, which would serve as the missing link in the complex pathogenesis of this disease.”
SARS‐CoV‐2 is presumed to multiply in alveolar (lung) epithelial cells which express the ACE2 receptor. In this setting, the virus causes lung damage while simultaneously infecting alveolar macrophages and inducing local inflammation. Subsequently, the main cause of COVID‐19 ARDS is attributed to an immune system collapse, or “cytokine storm,” which leads to severe ARDS and destroys the lung cells. Recently, clinicians and researchers have questioned whether endothelial disorders may cause early thrombosis, which would later complicate ARDS. An earlier study of 183 COVID‐19 patients in China found small blood clots throughout the systemic blood vasculature in 71% of those who died. Again, to simplify, all lung and heart vulnerabilities that are associated with death from COVID 19 are connected via the health (or lack thereof) of the glycocalyx.
Risks of a Damaged or Destructed Glycocalyx
There are numerous serious risks associated with a glycocalyx that has been significantly damaged or destroyed. These include
Edema (swelling of the body’s limbs)
Thrombrosis (blood clotting)
Potential elevated risk for death from SARS CoV-2
exposure of endothelial cells to oxidative damage
vascular hyperpermeability that may result in sepsis
Vascular damage relating to sustained hyperglycemia
Poor digestion and absorption of nutrients
Reduction of nitric oxide levels in the body
Increase of susceptibility to self tissue attack/autoimmune disease
Complement activation and kidney stress (a process of immune response with transplantation, including prostheses such as artificial joints)
So, how does the glycocalyx become damaged or destructed? The major causes are hyperglycemia, oxidative stress, and inflammatory stimuli, such as in a severe immune reaction that does not resolve. High levels of TNF-alpha that are produced in such inflammatory states are very destructive to the glycocalyx. Age and time may also play a role in its damage.
The Bottom Line
To make sense of the importance of this structure in the body and its relevance to key balances and functions, I use the analogy that loss of the glycocalyx is like having peanut butter stuffed up your nose. As it relates to blood, circulation, absorption of nutrients and immune response, everything is dependent upon clean, open lines and the ability to get junk out and good stuff in.
We must work diligently and fundamentally to heal any and all of the risk factors for a damaged/destructed glycocalyx, including the stabilization of blood sugar through proper nutrition, the stabilization of the immune system through investigation of pathogenic burdens and proper protocols for dysregulation, the balancing of the autonomic nervous system, anabolic/catabolic balancing, and the assurance of effective methylation processes for suitable nitric oxide production.
We also have the opportunity to utilize an incredible compound to support the healing of the glycocalyx. Rhamnan sulfate, a specialized sulfated polysaccharide derived from the green seaweed Monostroma nitidum is that compound. Some studies indicate healing of arterial elasticity through improved endothelial function of nearly 90% within 2 hours of consumption of the substance.
If you have a history of CV stress (or family history of CV disease), acute or chronic immune challenges, autoimmune disease, blood sugar dysregulation and/or diabetes, or simply age beyond 35, this may be an area of consideration for you/your health. It is important to stabilize with personalized nutrition, targeted testing and therapeutic protocols.
Please contact me today at Julie@truenaturehealthconsulting.com to learn more about this amazing compound and whether it might be right for your personal health protocol. We provide holistic teleheath services.
Non-linkable Resources
1) “Vulnerable Plaque Formation from Obstruction of Vasa Vesorum by Homocysteinylated and Oxidized Lipoprotein Aggregates Complexed with Microbial Remnants and LDL Autoantibodies”, Uffe Ravnskov and Kilmer McCully, 2009