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Our Endothelium, Free Radicals, Immune, and LDL in Health and Disease  Part 1 - April 14, 2022

Friends, this will be a two-part discussion with the second section related to dietary and lifestyle strategies.

The endothelium system, crucial for life, good health, vitality, and longevity, is an extensive, very thin layer of multifunctional squamous cells that lines, protect, our blood vessels, inside and out, as well as our heart, lungs, actually all our organs, including our brain and endocrine systems. 

The medical community had previously thought for a long time, that the endothelium was just a barrier that separates your blood from the tissue walls. But in 1980, a pharmacologist from New York named Robert Furchgott discovered it does much more than that.

Furchgott discovered that the endothelium controls your blood vessels. It makes them relax and dilate when you need more blood flow–when the endothelium doesn’t work well, blood flow is compromised, and thus one’s health, vitality oxygenation, and removal of cellular wastes are impaired.

It also cross-talks with our immune and skeletal system, especially bone density, in facilitating its function, adaptability, and health.
 
Significantly, in COVID, for instance, the endothelium is a very susceptible tissue to inflammation and micro clotting that infection and the subsequent cytokine storm, can lead to great morbidity and death–especially lung failure that could happen very rapidly, especially with those with any number of accompanying co-morbidities. 

Based on the total surface area, the endothelium is considered the largest organ in our body. If spread out, the cells would cover almost 2 football fields!  

The following select abstract excerpts bring greater insight into its relationship with the immune system.

Endothelium and Immune

SystemAdv Exp Med Biol

C. Sturtzel; 2017;1003:71-91.

“Endothelial cells are a constitutive part of the heart and vasculature and form a crucial link between the cardiovascular system and the immune system. Besides their commonly accepted roles in angiogenesis, hemostasis, and the regulation of vascular tone, they are an essential and active component of immune responses. The expression of a range of innate pattern recognition receptors allows them to respond to inflammatory stimulation, and they control immune cell recruitment and extravasation into target tissues throughout the body…. endothelial cell properties and functions and cross-talks with the immune system as well as the operational immunological role of endothelial cells in facilitating immune responses”.

Other possible signs of a sluggish endothelium often thought just to be aging, are declining
 
vision, aches, pains in the knees or other joints, or an increase in blood pressure or cholesterol levels.
 
However, the following comments are crucial in the development of heart disease. That is the oxidation of one’s LDL cholesterol. 

Actually, as an aside, a fascinating principle is that the body will do everything possible, to avoid “oxidative stress and damage to its DNA”! 

It will throw itself in front of “free radicals” so to speak, if dietary and powerful cellular antioxidants are not enough, to protect your DNA –a biological evolutionary imperative.

So, perhaps what we consider a disease process, oxidized cholesterol as the first step in heart and vessel disease,  is actually the lesser of two evils from the standpoint of Nature in prioritizing the procreation of a species over its temporal health!

 Still, LDL oxidation is far from trivial.

The oxidation of LDL is thought to occur when LDL cholesterol particles in your body react with free radicals; unstable molecules that are produced as a result of normal metabolism, a disease, or exposure to toxins.

Free radicals cause oxidation, a type of chemical destabilization of molecules such as LDL cholesterol. The oxidized LDL itself then becomes more reactive with the surrounding tissues, especially the endothelium inside blood vessels, which can produce inflammation, disease, and organ damage and is a threat to your cardiovascular health.

LDL cholesterol molecules are not all the same size, and some are larger than others. Smaller LDL particles are more likely to become oxidized, making them more detrimental to your health.

Bhattacharyya noted that reactive oxygen species (ROS) are also produced within the gastrointestinal (GI) tract since ingested materials and microbial pathogens can induce oxidative injury and GI inflammatory responses involving the epithelium. endothelium, and immune/inflammatory cells. 
 
But here again, we may be a bit fooled in that free radicals, usually the bad guys, also have a protective role in working with the immune system against pathogens and even fighting cancer cells ( for instance as generated through the treatments of cancer by radiation).

We can see and appreciate how systems do not operate as independent entities, what is good is not always bad, and there are complex crossovers and tie-ins with cellular and physiological functions in so many ways that we still and will continue to discover new concepts of interactions that will actually allow us in our understanding and research to find new important therapeutics and drug discoveries.

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