- The effects of a heart attack are often permanent, unlike some other tissues, heart tissue cannot regenerate.
- This means that even if someone survives a heart attack, the damage done may cause health problems or death in the years after the event.
- Regenerating heart tissue to treat damaged heart tissue is a hot topic in research.
Now researchers have discovered a mechanism that allows them to treat heart tissue in mice, before a heart attack, in a way that provides protection months after.
Although most people initially survive a heart attack from a reliable source, the risk of death increases significantly in subsequent years.
In fact, 65% of people over the age of 65 who have a heart attack will die within eight years of the first event, according to a reliable source. This is at least in part because a person can survive an initial heart attack, the heart attack itself, which causes heart tissue to become deprived of oxygen and then die, which cannot regenerate in adult humans.
In a recent animal study, researchers identified a mechanism that allowed them to treat heart tissue and make the hearts of healthy mice more resilient before a heart attack.
Heart attack and muscle death
Professor James Leeper, Ph.D., is Associate Medical Director at the British Heart Foundation and Professor of Molecular Medicine at the School of Cardiovascular and Metabolic Health at the University of Glasgow, U.K.
"Most heart attacks are caused by coronary artery disease, which can narrow your heart's arteries. The narrowing is caused by a gradual buildup of fatty deposits called atheroma. If a piece of atheroma breaks off, a blood clot forms around it to repair the damage to the artery wall. This clot can block your coronary arteries, This starves the heart muscle of blood, oxygen and vital nutrients, leading to death of the heart muscle.
The amount of damage to the heart muscle depends on the size of the area supplied by the blocked artery. Because the heart muscle cannot regenerate, it cannot fully repair itself. Instead, scar tissue forms in place of healthy heart muscle.
Cardiomyocytes are a type of cell in the heart that is responsible for muscle contraction. This contraction of the muscles is necessary to squeeze blood around the body of the heart, in response to the electrical signaling that regulates the heartbeat. When these cells are damaged in a heart attack, the heart loses its ability to effectively pump blood around the body.
Cardiomyocytes can proliferate in human embryos, an ability that is lost in mature adult humans. This is believed to be due in part to an evolutionary trade-off in which mature cardiomyocytes see the ability to increase deceleration with contractile force. This means that damage caused by events such as heart attacks cannot be repaired.
Healing challenges after a heart attack
The maturation stages through which cardiomyocytes move from embryonic to adult cells have been the focus of much research. Since cardiomyocytes cannot proliferate after damage caused by a heart attack, research has been done on how cardiomyocytes can be re-differentiated to a stage where they can proliferate. Elucidating the mechanisms surrounding this will provide information about how heart tissue damage can be reversed.
However, previous research on dedifferentiated cardiomyocytes has shown that the deleterious and lethal effects of irreversible dedifferentiation occur. This is because dedifferentiated cells are more likely to proliferate in a manner similar to cancer.
Redifferentiation of cardiomyocytes back to their pre-differentiation state is thought to prevent some of these complications. However, it is unclear whether the potential beneficial effects of earlier differentiation persist to a more proliferative state.
Treating the heart before an attack
Researchers in Dr. Eldad Tzahor's lab in the Weizmann Institute of Science's Department of Molecular Cell Biology previously identified a reliable source, when a specific protein coded by the ERBB2 gene, ERBB2, was overexpressed, and the division occurred. However, cardiomyocytes in this isolated, more proliferative state have a limited ability to contract. When the overexpression stopped, the researchers observed that the cardiomyocytes redifferentiated and returned to their original contractile capacity, and heart function improved.
In the lab's latest research, Dr. Avraham Shocked, Ph.D. Led by, they sought to investigate the mechanism behind this gene and protein and the longevity of its effects. They showed that when a transgenic mouse that transiently activated the ERBB2 gene at 3 months of age had a heart attack 5 months later, it recovered.
