The Real Cause of Heart Disease? part 2 of 4

By Uffe Ravnskov MD

The foam cell
Now it is time to introduce the foam cell, an important actor in the process of atherosclerosis. The foam cell is a type of white blood cell called a macrophage, but it doesn't look like a normal macrophage.

Its interior is filled with small bubbles that give the viewer the impression that it is loaded with foam. It isn't foam, however, it is lipid droplets.

Like many other white blood cells, macrophages are able to take up foreign material, such as bacteria and viruses, but also normal molecules that have been damaged, like oxidized LDL molecules. At least it is said so, because it is a necessary assumption to be able to explain how foam cells are created.

Foam cells mount up in rows just beneath the endothelial cells and are visible with the naked eye as yellowish stripes on the inside of the larger arteries. In the surrounding tissue outside the cells there are also many lipid droplets. The usual interpretation is that these droplets represent oxidized LDL cholesterol, identical with those seen inside the macrophages.

All people, even fetuses, have fatty streaks in varying amounts, and their number increases after birth. Later in childhood fewer are seen, but their number increases again in young adults. Elderly people have few fatty streaks, but more atherosclerotic plaques. (7)

Fatty streaks are considered as an early stage of atherosclerosis because they are often seen at the same places in the arteries where the atherosclerotic plaques usually are situated later in life. However, that small children have fewer fatty streaks than newborns tells us that they also may be temporary.

We think that fatty streaks is a normal and harmless phenomenon. The question is whether some of them turn into atherosclerotic plaques and why.

It is necessary to assume that the LDL molecules in the droplets are oxidized before they are taken up by the macrophages because like other cells, the macrophages do not take up normal LDL molecules.

Uptake of cholesterol demands that the cholesterol door, the LDL receptor, is open, and it doesn't open unless the cell needs extra cholesterol. The macrophage is said to have a backdoor, however, through which foreign guests, for instance oxidized LDL, can enter.

Another possibility, which we consider more likely, is that the droplets are taken up by phagocytosis. This is the way in which white blood cells engulf and destroy microorganisms and for a special reason it may work in this way with the lipid droplets as well. I shall soon tell you why.

The contradictions
The mechanism I have described above is in conflict with most of what has been observed in this field of medical science. I have mentioned most of the contradictions previously, but it is worthwhile to do it again and again and again.
Why do people with low cholesterol become just as atherosclerotic as people with high cholesterol?
Why do people with high cholesterol live the longest?
Why is high cholesterol not a risk factor for women?
Why is the degree of endothelial dysfunction the same in people with high cholesterol as in people with low? (8)
Why do normal cells oxidize normal LDL molecules?
Endothelial dysfunction is pronounced in atherosclerotic children who are born with excessive amounts of homocysteine in the blood, so-called hyperhomocysteinuria. Why isn't there any cholesterol present in their arteries? (9)

Furthermore, no one has explained how the dangerous bubbles, which Falk found in the artery walls, are created. Therefore, let me describe them in more detail.

The vulnerable plaque
Under the microscope the interior of the bubble is a mass of dead tissue containing lots of red and white blood cells, cholesterol crystals and lipid droplets looking just like those lying inside the foam cells.

Also viewed under the microscope, the vulnerable plaques look like bubbles in the endothelium, only separated from the interior of the arteries by a thin membrane. They can be seen in other arteries as well, for instance in the carotid arteries, those that transport blood to the brain.

By use of a catheter pushed into the arteries and provided with a thermometer in the tip, it has been shown that their temperature is a little higher than that of the surrounding tissue. (10)

Another interesting finding is the numerous lipid droplets that are found in the inflamed arterial wall outside the vulnerable plaques. They are rarely seen directly beneath the endothelium like the foam cells, as should be expected if LDL cholesterol entered via the endothelium, but much deeper. (11)

This observation is crucial for the understanding of our hypothesis. But before I go into more detail it is necessary to tell you more about the lipoproteins. Most researchers today think that their main function is to carry cholesterol, but they also have other important functions.

The lipoprotein immune system
Sixty years ago researchers discovered that the lipoproteins participate in our immune system by binding and inactivating bacteria, viruses and their toxic products. (1)

The lipoprotein immune system may be particularly important in early childhood, because in contrast to the antibody-producing system, which needs repeated stimulations to function properly, the lipoproteins work immediately and with great efficiency.

There are many ways to demonstrate it. For instance, researchers have looked at mixtures of lipoproteins and bacterial toxins with an electron microscope. What they saw was that the toxin molecules stuck to each other and became attached to the LDL molecules. (12) Similar experiments with a virus gave the same result. (13)

In the laboratory it has been shown that human LDL is able to inactivate more than 90% of the most toxic bacterial products.(14) When Kenneth Feingold and his coworkers at the University of California in San Francisco reduced blood cholesterol in rats and gave them an injection of bacterial toxin, most of them died quickly but if they injected a purified human LDL beforehand, they survived.(15) Mihai Netea and his team from the University Hospital in Nijmegen found that this is not necessary if they used mice with familial hypercholesterolemia. Most of such mice survived, whereas normal mice died immediately. (16)

When we are attacked by microbes, the white blood cells send a message to the liver by excreting their hormones, the cytokines. The liver responds by increasing the production of lipoprotein including the ‘bad' LDL; yet another indication that LDL is a useful molecule.

Most surprising is that apart from those who have been directly involved in the research in this field, very few know anything about this system, not even experts in infectious diseases or immunology, and hitherto I have not found a word about it in any current textbook.

The Real Cause of Heart Disease? Part 3

Dr. Uffe Ravnskov MD

Author of "The Cholesterol Myths" and "Fat and Cholesterol are Good for You"
Creator and spokesman of THINCS, "The International Network of Cholesterol Skeptics"

1. Ravnskov U, McCully KM. Ann Clin Lab Sci 2009;39:3-16.
    A short version in Swedish is available in Medicinsk Access 2009;2:15-8.
7. Klotz O, Manning MF. J Pathol Bacteriol 1911;16:211-20.
8. Falk E. Br Heart J 1983;50:127-34.
9. Stary HC. Atherosclerosis 61987;4:91-108.
10. Stary HC.Arteriosclerosis1989;9(Suppl 1):119-32.
11. Reis SE and others. Am Heart J 2001;141:735-41.
12. McCully KM. Am J Pathol 1969;56:111-28.
13. McCully KM. Clin Chem Lab Med 2005;43:980-6.
14. Madjid M and others. Am J Cardiol 2002;90(10C):36L-39L.
15. Guyton JR, Klemp KF. Am J Pathol 1993;143:1444-57
16. Bhakdi S and others. J Biol Chem 1983;258:5899-904.

September 2011 

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