- While skin, bone, and other tissues in the human body can repair themselves after injury, the heart lacks this ability.
- Using a mouse model, researchers from the University of Pittsburgh Medical Centre 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 stresses, but at the same time may also prevent the heart from having the ability to regenerate.
Heart cells rapidly divide during embryonic and fetal development to form cardiac tissue and the myocardium. But when heart cells mature in adulthood, they reach a terminal state where they can no longer divide.
A new laboratory research study published in
The researchers found that quieting 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 quieting may also prevent the 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 in tiny pores that allow information to move 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 goes down. They decreased by 63% across 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, as the number of nuclear pores controls the amount of information in the nucleus. The researchers noted that as heart cells mature and the nuclear pores decrease, less information gets inside.
In previous research, the research team found that a gene called Lamin 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 survival than mice with more nuclear pores.
In response to stress, such as high blood pressure, the heart cells receive signals into their nucleus that modify gene pathways, leading to structural changes in the heart. This remodeling is a major cause of heart failure.
The findings in this research may help explain how nuclear pores contribute to the remodeling process.
Medical News Today interviewed lead author Dr. Bernhard Kühn, associate professor of pediatrics and director of the Pediatric Institute for Heart Regeneration and Therapeutics at Pitt School of Medicine and UPMC Children’s Hospital of Pittsburgh.
Dr. Kühn explained the key findings of this research to MNT:
“The paper shows how mammalian heart muscle cells, as they achieve adulthood, progressively reduce the number of pathways by which they communicate with their environment. While this protects them from damaging signals, such as stress, it comes at a cost, because the reduced number of communication pathways also limits beneficial signals, for example, signals to regenerate itself.
As such, this paper provides an explanation for why adult hearts do not regenerate themselves, but newborn mice and human hearts do.”
Dr. Kühn highlights that “although the paper shows significance in a mouse model of hypertension, a direct indication for improving the lives of patients with high blood pressure is not given. Nuclear pores are very large protein complexes, and they are very, very hard to target therapeutically with the currently available drugs.”
Dr. Kühn said while further research is needed, the new research provides “fundamental insight that stress response and regenerative response in the heart are coupled.”
“It lays the foundation for future research that will be directed 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 may lead to translational research that can ultimately benefit patients.
MNT also spoke with Dr. Ronald Grifka, board certified pediatric cardiologist and Chief Medical Officer with the University of Michigan Health-West, not involved in this research.
“[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. How the environment interacts with our body is generating much interesting research.” Dr. Grifka said.
“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 modifies our responses can be helpful in deciding if 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 high blood pressure is important, although more research will be needed to determine how much regeneration may be compromised.
– Dr. Ronald Grifka
Nancy Mitchell, registered nurse and contributing writer at Assisted Living, highlighted to MNT that findings from laboratory research take a long time before they can be applied directly to patients.
When asked if laboratory research can lead to the development of new medicines, Mitchell said, “it may take up to two decades for cardiovascular treatments to make it to the [patient’s] bedside.This is because most of these research studies began as animal-tested trials. They then need to undergo human testing, which is no two-step task. Human studies on heart health often involve active investigations with carefully selected population demographics.”
“Many studies span multiple years to yield valuable results, especially with heart-related conditions,” she added. “It can be complicated because cardiovascular diseases like hypertension tend to have multiple underlying factors that can affect the progression of the disease over time.”
Finally, Dr Grifka noted that “this type of translational research often requires several years of studies and close follow-up before it reaches widespread clinical use.”