Introduction:

The deadly atherosclerotic plaque develops in areas of tissue damage, including in heart and artery elements. Such areas are called crystallization centers. The structure and composition of this plaque is diverse. Cholesterol-phosphate plaques with variable proportions of both components predominate (1–24), regardless of the place of formation.

External wounds and tissue damage (e.g. skin) heal spontaneously. This mechanism is well understood.   

The areas of damage to the heart or arterial tissues also heal spontaneously, but in a different way. They “attract” nearby charged ions, initiating the construction of atherosclerotic plaque. These ions can be organic (cholesterol) as well as calcium cations, phosphate ions, etc. The ions attached to such a crystallization center act as an adhesive tape “sealing” the site of damage. This phenomenon of self-healing of damage to the heart and arteries is the subject of the presented article.    

Research findings:

Valves:

Valve examinations typically focus on their elements removed surgically due to various types of heart disorders. Studies of such samples present the results of valves that are often already significantly changed as a result of secondary processes. This does not allow for observation of the first stages of changes in the structure of, for example, valve leaflets. One of the possibilities of detecting early changes in valves is using valves from a valve cryobank.

Examinations of these valves using a scanning microscope allowed for the identification of changes (damage) in the structure of the leaflets and the earliest stages of development of calcifications and atherosclerotic plaque (Photo 1, 2).

Photo 1: A, B – aortic valve leaflets with delaminated (damaged) aggregates of collagen fibers (blue arrows) constituting the centers of formation of “calcifications” (red arrows) and atherosclerotic plaque. B – scanning microscope, magnification according to scale.

Early stages of biomineralization of damaged heart elements are visible only at significant magnifications, especially in places of submicroscopic damage to the biological structure of heart tissues (Photo 2).

Photo 2: Fragment of a mitral valve shown at high magnification, in the area of early phase of cholesterol mineralization development, with grains of < 0.1 µm (red arrows). Scanning microscope, magnification according to scale.

Arteries:
Atherosclerotic plaque most often develops in places of damage to the intima. This can be observed with a biological microscope in histological preparations, after computer magnification of images (Photo 3 A). The observed deformations of the intima, its delamination and sometimes separation from the artery wall, are areas where atherosclerotic plaque develops. Its structure is diverse, and one of the most common forms is an internal aggregate structure (Photo 3 B).

Photo 3: A – I (blue arrow) – intima on the inner wall of the aorta. 1 – the earliest phase of atherosclerotic plaque formation, just below the surface of the damaged intima. 2 – damaged intima. 3 – delaminated intima. B – image of the aortic wall covered at the site of damage with a thick atherosclerotic plaque of aggregate structure. Arrows show the surfaces of the partially destroyed aortic wall. Biological microscope, preparations stained with chematocycline, magnification according to scale.

Biomineralization center and mechanism of formation of atherosclerotic plaque:

The elements necessary for the formation of atherosclerotic plaque are the biomineralization center and cholesterol molecules (electrically charged), as well as calcium ions and phosphate ions.

Atherosclerotic plaque begins in the biomineralization center, i.e. at the site of damage to the aorta or valve. In this place, broken ionic bonds with electrical charges occur in the tissues (Fig. 1 A, B). There are many causes of damage (and creation of biomineralization centers). They can be genetic, caused by infections, excessive physical exertion, polluted environment, etc.      

Figure.1: Diagram of the formation of atherosclerotic plaque.

A – damage to the inner wall of the artery. B – magnification of the area with destroyed intima (center of biomineralization – plaque formation) built of polar phospholipids. Places of destruction of interatomic bonds endowed with electrical charges attract and attach ions flowing in the blood.

Mechanism of repair (self-healing) of heart and arterial damage:

The identified mineralization of micro-damaged areas of heart and arterial tissues is only recognizable in a scanning microscope at high magnifications. In the elements of the heart valves, the damaged areas begin to mineralize with calcium phosphate crystals <0.1 μm in size. Their crystallization begins at the edges of the damaged area and develops, “overgrowing” the entire damage (Photo 4 A).

Cholesterol crystallizes quite differently in the damaged areas. It forms individual, slowly growing plaques or plaque aggregates (Photo 4 B). This leads to the “overgrowing” of the damaged area, but the process of increasing cholesterol concentration (plaque) is not stopped. There is often a dysfunction of this element of the heart.

Often, in the areas of overgrowth of the damaged spots, mixed substances occur – cholesterol-phosphates with different proportions of both components.

Photo 4: A – aortic valve leaflet damage (blue arrows) overgrowing at the edges with calcium phosphate microcrystals. First stage of self-healing of damage (red arrows). B – mitral valve damage (blue arrows) in which self-repair of damage with cholesterol plaques (red arrows) develops. Scanning microscope, magnification according to scale.

Self-healing of arterial damage leads to scarring, but further development results in the formation of dangerous atherosclerotic plaque.

The earliest phases of “self-healing” of damage to the inner surface of arteries were observed as the formation of collagen fibers overgrowing the damaged area (Photo 5 A). Observations conducted at higher magnifications show that these fibers combine to form atherosclerotic microplaque (Photo 5 B).

Photo 5: A – early stage of self-healing of damage to the inner surface of the artery. Collagen fibers “overgrow” the site of damage. B – atherosclerotic plaques (arrows) in the early stage of formation at the site of damage to the intima. Scanning microscope, magnification according to scale.

Summary:

One way to combat atherosclerotic plaque is to focus on dysfunctions in the organs that determine the excess of substances mineralizing crystallization centers. This means, for example, combating liver dysfunctions that result in increased cholesterol in the blood. Another example is normalizing the functioning of the thyroid and parathyroid glands that determine the production of calcitonin and parathyroid hormone, which in turn stabilize the level of Ca²⁺ ions, etc.

Another method of combating atherosclerosis may be prevention, i.e. stopping damage (and creation of plaque formation centers) from occurring.

There are a number of potential methods for eliminating factors that contribute to tissue destruction. One of them is undoubtedly the rapid elimination of infections (e.g. with antibiotics), which reduces the amount of toxins secreted by infecting microorganisms. Consequently, it reduces the risk of these toxins destroying tissues, i.e. the formation of crystallization centers.

Attempts to block these centers, i.e. to deprive them of electrical charges, are important. The phenomenon can be, figuratively speaking, compared to patching holes in tires. Administering an appropriate substance could cause a compound to be found in the crystallization center that will eliminate the possibility of plaque formation.

The presented results of studies on damaged elements of the heart and arteries indicate that the body heals (repairs) the places of damage itself, creating atherosclerotic plaque. In arteries, the places of damage to the artery wall and endothelium begin to overgrow with collagen microfibers or become covered with phosphate aggregates.

Unfortunately, this stage of self-healing of damage (the first stage of atherosclerotic plaque formation) does not stop. The atherosclerotic plaque continues to develop, resulting in the effects we all know.

While further research is needed, it is probably possible to find ways of stopping the development of atherosclerotic plaque at the initial stage of blocking tissue damage. To do this, the problem of preventing the surface of the forming atherosclerotic plaque from further attachment of cholesterol and other ions must be solved.

The presented idea requires extensive testing, of course. Perhaps the solution will be properly prepared collagen, administered intravenously as a very diluted suspension. It can both crystallize in the crystallization center and “repair” the destroyed tissue, as well as block further development of the atherosclerotic plaque.