Home Cellular science Clues to why adult hearts aren’t regenerating

Clues to why adult hearts aren’t regenerating

  • While the skin, bones and other tissues of the human body can repair itself after injury, the heart does not have this ability.
  • Using a mouse model, researchers at the University of Pittsburgh Medical Center studied how heart cells communicate, involving cellular signals.
  • They found that the number of communication pathways decreases as heart cells mature in mice. This process may have evolved to protect the heart from stresses, but at the same time may also prevent the heart from having the ability to regenerate.

Heart cells divide rapidly during embryonic and fetal development to form heart tissue and myocardium. But when heart cells mature into adulthood, they reach a terminal state where they can no longer divide.

A new laboratory research study published in Development Cell investigated the biological pathways behind this terminal state.

Researchers have found that quieting the communication between heart cells and their environment protects the heart from harmful signals related to stresses such as high blood pressure. But at the same time, this calming can also prevent heart cells from receiving signals that could promote regeneration.

The researchers looked closely at the nuclear pores of mouse heart cells (cardiomyocytes).

The nucleus is surrounded by a nuclear envelope, an impermeable protective layer, and is lined with tiny pores that allow information to move.

The study involved super-resolution microscopy, a type of biomedical imaging, to examine and count the number of nuclear pores.

Researchers have found that as cells mature, the number of pores decreases. They decreased by 63% during development, from an average of 1,856 in fetal cells to 1,040 in infant cells to just 678 in adult cells.

This finding is significant because the number of nuclear pores controls the amount of information in the nucleus. The researchers noted that as heart cells mature and nuclear pores shrink, less information gets inside.

In previous research, the research team discovered that a gene called Lamina b2 was involved. This gene, important for cardiomyocyte regeneration, is highly expressed in newborn mice but declines with age.

In this study, mice were engineered to express fewer nuclear pores. These mice had better heart function and better survival than mice with more nuclear pores.

In response to stress, such as high blood pressure, heart cells receive signals in their nuclei that alter genetic pathways, leading to structural changes in the heart. This remodeling is a major cause of heart failure.
The results of this research may help explain how nuclear pores contribute to the remodeling process.

Medical News Today lead author interviewed Dr Bernhard Kuhnassociate professor of pediatrics and director of the Pediatric Institute for Heart Regeneration and Therapeutics at the Pitt School of Medicine and UPMC Children’s Hospital of Pittsburgh.

Dr. Kühn explained the main results of this research to DTM:

“The paper shows how mammalian heart muscle cells, as they reach adulthood, gradually reduce the number of pathways through which they communicate with their environment. Although this protects them from harmful signals, such as stress, it comes at a cost, as the reduced number of communication pathways also limits beneficial signals, for example, signals to regenerate.

As such, this article explains why adult hearts do not regenerate, but newborn mice and human hearts do.

Dr. Kühn points out that “although the article shows significance in a mouse model of hypertension, a direct indication for improving the lives of patients with arterial hypertension is not given. Nuclear pores are very large complexes proteins, and they are very, very difficult to target therapeutically with currently available drugs.

Dr Kühn said that although more research is needed, the new research provides “fundamental insight that the stress response and the regenerative response in the heart are coupled”.

“This lays the groundwork for future research that will aim to decouple these mechanisms,” he added. “How could we make a human heart regenerate without increasing its sensitivity to stress?

Laboratory research of this nature can lead to translational research that can ultimately benefit patients.

DTM also spoke with Dr. Ronald Grifkaboard-certified pediatric cardiologist and chief medical officer of the University of Michigan Health-West, not involved in this research.

“[As] medical research is becoming more sophisticated, we are learning more and more about the interdependence between various organs and how they influence each other. Many interactions have a positive response; sometimes there is a negative response. How the environment interacts with our body generates a lot of interesting research. says Dr. Grifka.

“Stress can affect many parts of the body and the interactions can be very complicated,” Grifka explained. “Understanding how stress interacts with various organs and what alters our responses can be helpful in deciding whether treatment is needed and, if so, which treatment is most effective.”

“In this study, describing how heart cells interact with the environment, controlling stress and blood pressure is important, although further research is needed to determine the extent to which regeneration may be compromised.

– Dr. Ronald Grifka

Nancy Mitchellregistered nurse and contributing writer at Assisted Living, pointed out to DTM that the results of laboratory research take a long time before they can be applied directly to patients.

When asked if laboratory research could lead to the development of new drugs, Mitchell said: “It may take up to two decades for cardiovascular treatments to reach the [patient’s] bedside.Indeed, most of these research studies began with animal testing. They must then undergo human testing, which is not a two-step task. Human studies of heart health often involve active surveys with carefully selected demographic data.

“Many studies span several years to yield valuable results, especially with heart conditions,” she added. “It can be complicated because cardiovascular diseases like hypertension tend to have multiple underlying factors that can affect disease progression over time.”

Finally, Dr. Grifka noted that “this type of translational research often requires several years of study and close follow-up before reaching widespread clinical use.”