I have entitled this little series ‘What causes heart disease?’ But I have been at pains to point out that you cannot possibly establish potential causes heart disease, until you are clear about the underlying process.
By this I mean you can say that smoking causes heart disease – and you would be right. You can also say that Systemic Lupus Erythematosus (SLE) causes heart disease – and you would also be right. You can say that type II diabetes causes heart disease – and you would be, guess what, right. You could say that obstructive sleep apnoea causes heart disease and you would be… right again. Steroids…right again. High levels of fibrinogen…right once more. Cushing’s disease…right. Depression… bang on the button.
But you have to be able to answer the question, how can these very different things lead to the same disease? Or, perhaps you are going to argue they all cause different diseases, that look exactly the same? If so we are doomed, as this would mean that there are a hundred different types of heart disease each with their own individual cause. (I believe this to be unlikely, and am not further discussing it as a possibility).
In short, you cannot simply go around stating that you have identified cause after cause, after cause after cause. Or you can, but it does not help in the slightest with understanding what is going on. It just becomes increasingly confusing. You must establish the process, or processes, that can link all of these potential causes together. Until you can answer this, you are basically just floundering about.
I spent thirty years floundering about in this unending kaleidoscope of risk factors before I decided that it was mission critical to work out what was the actual disease process underpinning CVD. In the end, it came down to this.
The four stage process
Heart disease – or the development of atherosclerotic plaques, followed by the final, fatal, blood clot – consists of four stages. These stages obviously overlap, and interact, and separating them out is a somewhat artificial process. However, I think a degree of separation is necessary for understanding. You can jumble them all around again afterwards.
I should also say that; in this particular blog, I am only going to look at the first stage of the four stage process. And the first stage is endothelial damage.
The endothelium is a single layer of cells that lines all arteries, and veins. At one time endothelial cells were believed to be essentially inert. They just sat there, lining the blood vessels, and not doing much. But, of course, these cells are gigantically, mind-bogglingly, complex.
However, for the sake of this discussion, I am only going to look at three aspects of endothelial cells.
- Nitric oxide synthesis
- What happens when endothelial cells are damaged
- Tissue factor
Nitric oxide synthesis
A critical role of endothelial cells is to manufacture nitric oxide (NO). When it comes to CVD, this little molecule is absolutely key. First, it relaxes the smooth muscle in artery walls, causing them to relax, which opens up the surrounding artery. This then lowers blood pressure.
Within conventional medicine various ‘nitrates’ are given to people with angina, which opens up the coronary arteries, improves blood flow and the oxygen supply improves. The first of these to be discovered was nitro-glycerine. Renamed glyceryl tri-nitrate, and put into tablets to dissolve under the tongue.
NO is also a very powerful anticoagulant – it stops the blood clotting. This is clearly essential as you do not want clots forming on normal blood vessel walls, and when NO levels fall, accidental blood clotting becomes a real possibility.
Healthy endothelial cells produce lots of NO. Stressed and damaged endothelial cells do not. Which means if you have stressed or ‘dysfunctional’ endothelial cells, your arteries are narrower ‘constricted’ and the blood within them more likely to clot.
In recent years it has been recognised that damage to endothelial cells is an early marker of atherosclerosis, as made clear in this paper, entitled: ‘Endothelial dysfunction: the early predictor of atherosclerosis.’
‘Endothelial dysfunction, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis.’ 1
Which means that damaged, or dysfunctional, endothelial cells can be recognised by their failure to produce NO. On the flip side, if there is abundant NO in the body this seems, in reverse, to keep endothelial cells healthy.
There are some drugs, supplements, and activities, that can actually increase NO synthesis in endothelial cells, and also the rest of the body. Possibly the most powerful single factor that can do this is sunlight. As highlighted in this paper, where the rather snappy title actually says all that needs to be said: ‘Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates.’2
Essentially, if you sunbathe, NO is released throughout the body, and your blood pressure drops (as your arteries open wider). Other studies have found many other major benefits of sun exposure on lung, breast, prostate and colo-rectal cancer, but that is a story for another day.
For now, the focus here is simple. Endothelial cells produce NO, this chemical is vital for CVD health. Any factor that reduces NO synthesis is unhealthy, any factor that increases NO synthesis will protect against CVD.
What happens when endothelial cells are damaged
I am not looking in any great detail here at how endothelial cells are damaged, although there are many, many, things that have a negative impact on the health and wellbeing of endothelial cells. High blood sugar, low blood sugar, steroids, smoking, cocaine, SLE, Obstructive Sleep Apnoea (OSA), and suchlike.
Perhaps the single most important factor that can damage endothelial cells is this – biomechanical stress. By biochemical stress I mean turbulent blood flow, stretching and bending of the blood vessel, high shear stress, high blood pressure, rapid blood flow, points where the blood has to change direction violently.
Violent direction occurs where smaller arteries branch off from larger one e.g. where carotid arteries (that supply blood to be brain) branch from the aorta at the base of the neck. Such points are called bifurcations, and bifurcations are where the biggest and most ‘vulnerable’ atherosclerotic plaques are almost always to be found.
In reality, extreme biomechanical stress only takes place in the larger arteries in the body, where the pressure is high and there are great forces for the endothelium to deal with. A raging white water river. Place a pebble on the side of this maelstrom and it will soon be ripped off and dragged downstream. Veins and the arteries in your lungs, on the other hand, are more like the lazy rivers of East Anglia, slowly meandering along through flat fields.
It is almost certain that the massive difference in the biomechanical stress that endothelial cells have to deal with, in arteries, in comparison to veins and pulmonary blood vessels (the blood vessels in the lungs) fully explains why atherosclerotic plaques never develop in veins and never develop in the pulmonary blood vessels (blood vessels in the lungs). Despite that fact that these blood vessels are exposed to exactly the same ‘risk factors’ as the arteries.
Moving on. It is possible to do more than simply stress endothelial. They can simply be stripped off. If and when this does happen, not only is there no NO at that location, something else far more important comes into play….
Sitting within all artery walls (and all vein walls too) is a substance called Tissue Factor (TF). It is by far the most powerful clotting agent known to nature. If you expose blood to it, a clot will immediately form, right on top.
This makes sense. If a large blood vessel is damaged, you will bleed to death very rapidly, unless a very strongly constructed blood clot forms right on top of the damaged area, to block the hole. Another point to mention is that TF triggers the ‘extrinsic’ clotting system which simply bypasses a large part of the blood clotting system. Clot right here, right now!
In truth, the system of blood clotting is incredibly complex, and I have not the slightest intention of covering it all here. Probably because I don’t fully understand it myself. However, at its simplest, blood clots consist of two key components. Platelets and fibrin.
Platelets are small ‘sticky’ cells. They are activated by exposure to Tissue Factor (TF), at which point they start clumping together to get the clot started. Whilst doing this they release about five hundred other substances that further activate the entire ‘clotting cascade.’ Then all hell breaks loose.
The end result of all of these clotting factors activating is that small strands of protein called fibrinogen are stuck together for form a long, very strong, string of protein called fibrin. This wraps round platelets, and anything else floating past, and binds everything together in a tight and very strong blood clot.
This clot then sticks very firmly to the site of damage, and grows, until all the damage is covered up. At which point the other five hundred factors that are designed to stop blood clots forming and/or getting too big, stop the clotting process in its tracks.
After the clotting process has been whipped into action, then brought to a halt, we have a blood clot stuck to the inside of the artery wall. Obviously if it grew too big it will have completely blocked the artery – resulting in a heart attack, or suchlike. Assuming, however, that it stopped growing, before completely blocking the artery. What then happens to it?
To be continued.