The first stage of cardiovascular disease is damage to the endothelium. The single layer of cells lining the arteries. After this, we need to look at what then happens? Before looking at this more closely, I would like to take you back in time around one hundred and sixty years. This was when the first scientific debates about plaque development were taking place.
Rudolf Virchow and Karl von Rokitansky were the proponents of different hypotheses at this time. I am grateful to Professor Paul Rosch for providing the information on Virchow’s ideas. He provided this description in one of his newsletter.
‘Rudolph Virchow was the first to demonstrate the presence of cholesterol in atheroma in 1856. He described atherosclerosis as “endarteritis deformans” The suffix “itis” emphasized that it resulted from an inflammatory process that injured the inner lining of the arteries, and that the cholesterol deposits started to appear subsequently
Virchow was very specific about this when he wrote. ‘We cannot help regarding the process as one which has arisen out of irritation of the parts, stimulating them to new, formative actions; so far therefore it comes under our ideas of inflammation, or at least of those processes which are extremely nearly allied to inflammation.
We can distinguish a stage of irritation preceding the fatty metamorphosis, comparable to the stage of swelling, cloudiness, and enlargement which we see in other inflamed parts. I have therefore felt no hesitation in siding with the old view in this matter, and in admitting an inflammation of the inner arterial coat to be the starting point of the so-called atheromatous degeneration and the cholesterol deposits came later.’
So, even one hundred and sixty years ago, eminent professors recognised that atherosclerotic plaques started with ‘inflammation of the inner arterial coat’ a.k.a…the endothelium. The cholesterol deposits came later. Quite so. Or to put this another way, the cholesterol was not the cause of the plaque, the appearance of cholesterol in a plaque was part of the second stage of plaque development.
However, whilst agreeing on this observation, Karl Von Rokitansky had a further hypothesis.
‘Rokitansky proposed that the deposits observed in the inner layer of the arterial wall were derived primarily from fibrin and other blood elements rather than being the result of a purulent process. Subsequently, the atheroma resulted from the degeneration of the fibrin and other blood proteins and finally these deposits were modified toward a pulpy mass containing cholesterol crystals and fatty globules.’
Or, to put it another way. He believed that plaques were, in fact, blood clots, in various stages of repair. He believed this because plaques looked exactly like blood clots, and contained everything that you can see in a blood clot. Perhaps most critically, a great deal of fibrin, which is the key component of all blood clots.
However, Virchow objected to this idea on the simple basis. ‘How can a blood clot form within the arterial wall?’ Or, how can a blood clot form under the endothelium. A good point, and Rokitansky had no effective response. So he lost.
However, there is a very simple explanation as to exactly how a blood clot can be found beneath the endothelium. And this is, because the endothelium wasn’t there when the clot formed. It grew over the top of the clot afterwards. Which takes us to Endothelial Progenitor Cells (EPCs).
After my last blog, a poster made the following comment.
‘And then… the clot, now trapped under the new endothelium, becomes plaque? If true, seems a stupidly “designed” :-) healing process.’
Well, superficially, this is a good point. Simply incorporating clot into arterial wall, where is forms a plaque and then kills you, does not seem a great idea. However, I would ask you to consider what would happen to a blood clot, lying on an artery wall, that simply broke off and travelled down the artery. What would happen?
The answer is simple; it would jam up as the artery narrowed. This could cause a stroke, or a heart attack, or suchlike. Exactly as happens with atrial fibrillation. Where small clots that break off from the atria travel into the brain and get jammed. The body does not like blood clots floating about in the arterial system.
So this does not happen/is not allowed to happen. When the endothelium is damaged, a clot forms on top of it. It is true that a certain amount/a great deal of this clot will be shaved away into very small (not stroke creating sized) pieces, but a ‘core’ will be left. This has to be got rid of in some way.
How are you going to do this? There is only one possible way. Firstly, you cover it over with another layer of endothelium, then you attack it, break it down, and destroy it. And this is exactly and precisely what the body does.
Once a blood clot has stabilized, Endothelial Progenitor Cells (EPCs), that are manufactured in the bone marrow, and float around in the bloodstream, are attracted to the clot. They stick to it, then they grow into fully mature endothelial cells, forming a new layer of endothelium, effectively drawing the clot inside the arterial wall. Then the clot is attacked and got rid of. How?
Well, a critical fact to add in here is that. EPCs do not always become endothelial cells, they can go down another developmental pathway as well. They can become monocytes, which in turn become macrophages. Macrophages are the ‘clear up’ cells of the immune system. They attack alien material and then engulf/ingest it. After this they either exit back into the blood stream or travel directly into the lymphatic system. Whereupon they are transported to lymph glands where they are broken down and all the ‘alien material’ is disposed of.
The body is amazingly clever is it not? After endothelium is damaged, and a clot forms, EPCs not only cover over the area of damage, they can also turn into the very cells that can clear up the clot/plaque and get rid of it. So, not a stupidly designed healing process at all. One of absolute brilliance. In fact, this is probably happening inside your artery walls right now.
The problems start to occur when the process of endothelial damage is occurring too rapidly for the healing system to clear up the mess. Repeated endothelial damage and clot formation over the same spot, time and time again. At which point, instead of having clot/plaque healing we end up with clot/plaque growth and development. Or as Rokitansky put it so eloquently
‘Subsequently, the atheroma resulted from the degeneration of the fibrin and other blood proteins and finally these deposits were modified toward a pulpy mass containing cholesterol crystals and fatty globules.’
Next, clot formation and associated problems.