2023-05-22 15:03:07
Researchers at the Hubrecht Institute have used zebrafish to explain their regenerative success. They discovered a new mechanism that acts as a switch to mature heart muscle cells during regeneration. Researchers at the LUMC subsequently showed that this mechanism had a very similar effect on human heart muscle cells and is therefore evolutionarily conserved. The results of the study show that studying natural heart regeneration in zebrafish and applying this knowledge to human heart muscle cells can contribute to the development of new therapies against cardiovascular diseases.
Damage to the heart
An estimated 18 million people die of cardiovascular disease every year. Many of these deaths are related to heart attacks. During such an attack, a brood plug impedes the supply of nutrients and oxygen to the heart. Cardiac muscle cells in the blocked part of the heart die as a result, leading to heart failure. While therapies exist to treat symptoms, there is a lack of treatments that replace lost tissue with functional, mature cells to cure patients.
Zebravis
Unlike humans, some animals such as zebrafish can regenerate their hearts. They recover their heart function within 90 days of injury. Surviving heart muscle cells manage to divide during this process, producing new cells. This unique mechanism is a source of new tissue for zebrafish to replace lost heart muscle cells. Previous studies have identified factors that can stimulate this heart muscle cell division. However, what happens to the newly formed heart muscle cells afterwards has not yet been studied. Researcher Phong Nguyen explains: “It is unclear how these cells stop dividing and mature so that they can contribute to normal heart function. We were intrigued that the new tissue in the zebrafish heart matured without problems and integrated into the existing heart tissue.”
Follow-up research
The results of the study showed that the regulatory substance LRRC10 promoted regeneration and that its role in calcium homeostasis can promote the maturation of heart muscle cells. This could help scientists who are trying to improve heart damage by transplanting cultured heart muscle cells into the heart.
While this potential therapy is promising, results show that the cells are still immature and unable to communicate with the rest of the organ. This leads to cardiac arrhythmias after transplantation. “More research is needed to define exactly how mature cultured cardiomyocytes are after treatment with LRRC10, but it is possible that an increase in maturation promotes the integration of transplanted cells,” says researcher Jeroen Bakkers.
Bakkers continues: “In addition, current models of heart disease are often based on immature cultured heart muscle cells. This could possibly be one reason why 90 percent of promising drugs ultimately do not reach the clinic. Our results indicate that LRRC10 can also improve these models.” LRRC10 could therefore make an important contribution to culturing cardiac muscle cells that are more similar to their counterparts in the adult human heart and thus promote the development of new successful therapies against cardiovascular diseases.
By: National Care Guide
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