Heart cell telomeres rapidly degenerate after birth, limiting the heart’s ability to recover after a heart attack, according to a new study. The findings – which were published in The Journal of Cell Biology by researchers at the Spanish National Center for Cardiovascular Research (CNIC) – suggest potential interventions that healthcare professionals could use to help the heart repair itself after a cardiovascular event.
While newborns have the ability to repair injuries to the muscle tissue of the heart – known as the myocardium – by the time we reach adulthood, much of these repair mechanisms have been lost. Because the cardiomyocyte cells in the heart are less able to proliferate and repair damage as they age, heart attack damage in adults tends to be permanent, potentially resulting in death.
Researchers at the CNIC set out to determine whether this cell cycle arrest phenomenon observed in the cardiomyocytes, was connected to the repetitive DNA sequences, known as telomeres, which form a protective cap at the end of chromosomes. As telomeres are susceptible to shortening with every cell replication cycle, cells can sometimes mistake these sequences for damaged DNA, which induces the cell to stop the replication process.
After measuring the length of telomeres in newborn mouse cardiomyocytes, the researchers found that these sequences quickly deteriorated in the first week of life. The researchers also noted a decreased in telomerase expression – the enzyme responsible for extending the telomeres – along with the activation of a DNA damage pathway and cell cycle inhibitor known as p21.
After further testing in mice deficient in the telomerase enzyme, they found that these animals had shorter telomeres compared to normal mice, and their cardiomyocytes stopped proliferating just one day after birth. In comparing heart injury in both wild type and telomerase-deficient mice, the researchers found that the cardiomyocytes in the shorter telomere mice were unable to proliferate and repair the damage done to the myocardium.
Interestingly, when the p21 cell cycle inhibitor was knocked-out, the regenerative capacity of the adult cardiomyocytes was significantly improved. These p21-deficient mice were better able to repair damage to the myocardium compared to wild type animals.
“We are now developing telomerase overexpression mouse models to see if we can extend the regenerative window,” said Ignacio Flores, senior author on the study. The researchers believe that maintaining telomere length in cardiomyocyte cells could help boost an adult’s ability to recover after a heart attack.