Clues to why adult hearts don’t regenerate

Clues to why adult hearts don’t regenerate

  • Although skin, bone, and other tissues in the human body can repair themselves after injury, the heart lacks this ability.
  • Using a mouse model, researchers at the University of Pittsburgh Medical Center investigated 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 stress, but at the same time it 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 the 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 studied the biological pathways behind this terminal state.

The researchers found that silencing communication between heart cells and their environment protects the heart from damaging stress-related signals, such as high blood pressure. But at the same time, this silencing can also prevent heart cells from receiving signals that could promote regeneration.

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

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

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

The researchers found that as cells mature, the number of pores decreases. They decreased by 63% throughout development, from an average of 1,856 in fetal cells to 1,040 in child cells to just 678 in adult cells.

This finding is significant, since 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 enters.

In earlier research, the research team found that a gene called lamina b2 He was involved. This gene, important for cardiomyocyte regeneration, is highly expressed in newborn mice but decreases with age.

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

In response to stress, such as high blood pressure, heart cells receive signals in their nucleus that modify genetic pathways, leading to structural changes in the heart. This remodeling is one of the main causes of heart failure.
The findings of this research may help explain how nuclear pores contribute to the remodeling process.

Today’s medical news main author interviewed dr bernard Kuhnassociate professor of pediatrics and director of the Pediatric Institute for Cardiac Regeneration and Therapeutics at Pitt School of Medicine and UPMC Children’s Hospital in Pittsburgh.

Dr. Kühn explained the key findings of this research to MNT:

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

As such, this paper provides an explanation for why adult hearts do not regenerate on their own, but newborn mice and human hearts do.”

Dr. Kühn highlights that “although the article shows importance in a mouse model of hypertension, no direct indication is given to improve the lives of patients with high blood pressure. Nuclear pores are very large protein complexes, and they are very, very difficult to target therapeutically with currently available drugs.”

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

“It lays the groundwork for future research that will be aimed at uncoupling these mechanisms,” he added. “How could we make a human heart regenerate without increasing its susceptibility to stress?”

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

MNT also spoke with Dr. Ronald Grifkaboard-certified pediatric cardiologist and medical director of the University of Michigan Health-West, who was not involved in this research.

“[As] As medical research becomes more sophisticated, we are learning more and more about the interdependence between various organs and how they affect each other. Many interactions have a positive response; occasionally there is a negative response. The way the environment interacts with our body is generating a lot of interesting research.” Dr. Grifka said.

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

“In this study, it is important to describe how heart cells interact with the environment, manage stress and high blood pressure, although more research will be needed to determine how much regeneration may be compromised.

– Dr. Ronald Grifka

nancy mitchellregistered nurse and contributing writer at Assisted Living, highlighted MNT that laboratory research findings 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 that “cardiovascular treatments can take up to two decades to reach the [patient’s] Headboard.This is because most of these research studies started out as animal trials. They must then undergo human testing, which is not a two-step task. Human studies of heart health often involve active investigations with carefully selected population demographics.”

“Many studies span multiple years to produce valuable results, especially with heart-related conditions,” he 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 it reaches widespread clinical use.”

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