Scientists talked about the mechanism of longevity of heart valves
Heart valves open and close tens of millions of times a year, maintaining their strength for decades. One of the mechanisms of their protection may be the very tension of the tissue during the work of the heart: with a certain load distribution, collagen becomes less vulnerable to the enzymes that break it down. How movement helps to preserve the structure of valves, why this protection can be disrupted in diseases, and what discovery means for the development of prosthetics — in the Izvestia material.
Millions of movements without stopping
There are four valves in the heart that ensure the movement of blood in the right direction. Their flaps open, allowing the flow to pass through, and close, preventing its return. The aortic valve is located between the left ventricle and the aorta, the largest artery through which blood enters the large circulatory system.
Even with a conditional frequency of 70 beats per minute, about 37 million heart cycles are gained per year. This is a calculated example that shows the scale of the work: the thin fabric must repeatedly change shape, withstand the load and continue to close tightly.
Collagen is largely responsible for the strength of the flaps. However, there are enzymes in the biological environment that can break it down, collagenases.
"Collagen is known to play a crucial role in maintaining the strength of heart valves, and their valves open and close millions of times a year. It is also known that there are collagenases in the fluid surrounding the heart that can destroy this collagen. Nevertheless, the flaps remain strong for decades," said Shadow Huang, the first author of the publication, associate professor of Mechanical and Aerospace Engineering at North Carolina State University.
According to her, the researchers were also interested in the opposite situation: in heart diseases, the integrity of the valves can be disrupted much faster. Scientists have tried to figure out what role tissue mechanics plays in this difference.
Strength depends not only on the composition
The authors combine the results of collagen research at different levels, from individual molecules to tendon tissues and heart valve flaps. Laboratory experiments with pig valve tissues form an important part of the argument.
Collagen in a living leaflet cannot be considered a fixed framework that has formed once and then only gradually wears out. The fabric maintains and renews its structure. In one of the experimental papers on which this line of research is based, the authors describe the balance between the removal of damaged collagen and the synthesis of new collagen.
Therefore, the very presence of cleavage enzymes does not mean pathology. It is important how quickly the fibers are destroyed and whether it is possible to maintain the structure necessary for the normal operation of the valve.
An additional difficulty lies in the structure of the fabric: the fibers are arranged in different directions, rotate when stretched and are not equally involved in the work. Changing the shape of the leaf as a whole does not mean that every collagen molecule experiences the same load.
That is why mechanical properties cannot be reduced to a single strength indicator. To evaluate enzyme protection, it is important to consider how the tissue stretches and how the force is transmitted inside it.
The direction turned out to be more important than simply increasing the load
In the experiments described by the university, the researchers varied the degree of stretching of the flaps, pulled the tissue in different directions, and varied the concentration of collagenase. After exposure, the microstructure of the samples was assessed to see if it was preserved or if there were signs of damage.
Two fundamentally different modes were compared. In one case, the stretching in two directions was not the same and maintained the ratio characteristic of the physiological work of the tissue. In another case, the samples were stretched equally along both axes.
This approach made it possible to check not only the effect of the amount of deformation, but also the value of its distribution. The two samples may experience stretching, but the condition of the collagen network inside them will vary.
While maintaining the physiological ratio of deformities, the researchers observed the protection of collagen. It was maintained under proven conditions both with increased stretching and with a higher concentration of the enzyme. When the ratio was changed, the collagen was destroyed at both tested levels of collagenase.
"We found that increased stretching did not damage collagen even with higher levels of collagenase, provided that the ratio of longitudinal and transverse stretching remained the same. When we changed this ratio, the collagen was destroyed regardless of the collagenase level," explained Huang.
This observation shows why the amount of enzyme alone does not explain the result. In the tested modes, the susceptibility of the tissue to its action also depended on how it was stretched.
How tension can block access to an enzyme
To explain the effect, the authors consider the mechanism of collagen stabilization by tension. According to this model, stretching changes the spatial configuration of the triple helix of collagen and may make the site available for enzymatic cleavage less accessible.
In other words, the chemical composition of a protein does not necessarily have to change in order for its stability to change. The shape of the molecule under load is also important. At the fabric level, this effect is complicated by the location and movement of the fibers. The same external deformation can be transmitted differently to individual elements of the collagen network. Therefore, the direction of stretching becomes part of the protection.
Previously, a similar effect was studied in collagen-rich tendon tissues. However, in such experiments, the fabric was usually stretched in one direction. Valve flaps operate in more difficult conditions: they deform in several directions at once.
"In previous studies, this protective mechanism was detected in collagen-rich tendon tissues, but there the tissue was stretched in only one direction. The flaps of the heart valves experience deformation in more than one direction with each opening and closing, so this result is a step forward," said the researcher.
Why Stronger doesn't mean Better
The protective effect does not give grounds to consider any increase in workload beneficial. In the review, the authors describe a more complex relationship: with moderate physiological tension, collagen's resistance to enzymes increases, and with pathological overload, destruction can accelerate again.
A V-shaped diagram is used for the explanation. It summarizes the results of different experiments and is not a single curve directly measured for all valves and all conditions.
In addition, the results of laboratory stretching of samples do not allow us to prescribe physical activity or determine a safe pulse rate. The paper investigated tissue deformation and its interaction with enzymes, rather than the effect of training on the service life of the valves.
What can happen in case of illness
According to the authors, a violation of the usual distribution of deformations helps to explain why in some diseases the valves begin to collapse faster. Changing mechanical conditions can deprive collagen of the protection that is maintained during normal tissue operation.
This leads to a possible sequence of events: a change in valve operation changes the load on its structure, and the increased vulnerability of collagen contributes to further damage. This is a mechanistic explanation that requires verification in relation to specific diseases.
The clinical disorders of the valves vary. As the US National Heart, Lung, and Blood Institute explains, with stenosis, the valve narrows and makes it difficult for blood to flow, and with regurgitation, part of the flow returns due to incomplete closure. The causes may be congenital or acquired, including those related to age and infections.
Therefore, mechanical protection of collagen does not explain all valve diseases. The work highlights one of the processes that can link load changes to tissue damage.
"Our results also help to understand why valves collapse so quickly when heart disease alters the deformity they experience: they lose this biomechanical defense mechanism," Huang said.
What can this teach prosthetic developers?
The practical prospect of the work is related to the creation of materials for the replacement of heart valves. Such a replacement is necessary when a damaged valve cannot be repaired. Existing prostheses solve the problem in different ways. Mechanical valves are made of durable artificial materials. They are usually more durable than biological ones, but require lifelong anticoagulant therapy. Biological prostheses are created from animal tissues, sometimes with artificial elements. Their durability is limited, and they may need to be replaced again over time.
For the development of new fabric materials, the results indicate an additional requirement: it is important to reproduce not only the shape of the valve, but also the features of its deformation. The material must open and close so that the collagen structure remains resistant to destruction.
The review also examines the preliminary mechanical conditioning of tissue engineering structures — the impact of a given load during their preparation. The authors associate this approach with the formation of a directed collagen structure resembling natural tissue.
So far, this is a research area, and not a proven way to extend the life of a human prosthesis. The presented work does not report on the clinical trial of the new valve and does not establish a period for which it could last longer than existing models.
"These results expand our understanding of how the heart works, how disorders occur, and how new biomaterials can be created to replace heart valves," Huang concluded.
For further developments, the transition from short-term protection of the sample to the durability of the entire structure is essential. It will be necessary to check whether the correct distribution of deformations is maintained during prolonged operation, after processing the material and in a living organism. This is what will make it possible to determine how suitable the discovered mechanism is for creating more durable valves.
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