心脏再生 z-bo 2020-12-17 378

　　A research paper entitled "Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation" was published online by Ignacio Flores, a researcher from the Spanish National Center for Cardiovascular Research, in the Journal of Cell Biology. The ends of chromosomes erode quickly after birth, which limits the ability of cells to proliferate and replace damaged heart tissue. This research and the paper also proposed potential new interventions that can improve the heart's ability to repair itself after a heart attack.

　　 Newborns can repair injured myocardium, but in adults, heart disease can cause permanent damage, which often leads to heart failure and death. Newborn mice can also regenerate damaged heart tissue. Their cardiomyocytes can proliferate and repair the heart in the first week after birth, but as the mice age, they lose this ability to regenerate, and most of their cardiomyocytes exit the cell cycle.

　　 Researchers want to know whether the cause of cell cycle arrest may involve telomeres, the repetitive DNA sequences that protect the ends of chromosomes. If telomeres grow too short—for example, because of the loss of a telomere-extending telomerase, the cell may mistake the end of the chromosome of the damaged DNA fragment, causing a checkpoint that inhibits the cell cycle to be activated.

　　 Therefore, Flores and his colleagues examined the chromosomal telomere length of the cardiomyocytes of newborn mice, and they found that the telomeres eroded rapidly in the first week after birth. This erosion is consistent with a decrease in telomerase expression, accompanied by a DNA damage response and the activation of a cell cycle inhibitor called p21.

　　 Compared with wild-type mice, telomerase-deficient mice have shorter telomeres, and the researchers found that their cardiomyocytes have stopped proliferating one day after birth. When Flores and his colleagues damaged the hearts of day-old mice, telomerase-deficient cardiomyocytes were unable to proliferate or regenerate the injured heart muscle. In contrast, wild-type cardiomyocytes can proliferate and replace damaged tissue.

　　 They also found that knocking out the cell cycle inhibitor p21 can prolong the regeneration capacity of cardiomyocytes and enable 1-week-old p21-deficient mice to repair damaged heart tissue more effectively than 1-week-old wild-type mice.

　　 Therefore, maintaining the telomere length of cardiomyocytes may increase the regeneration capacity of adult cells, thereby improving the recovery of heart tissue during a heart attack. Flores said: "We are now preparing telomerase overexpression mouse models to explore whether we can expand the scope of this regeneration."