The enzyme telomerase is known to repair various types of cell damage, and new results indicate that this activity can be exploited to prevent damage to heart tissue after acute injury such as a heart attack or myocardial infarction. The results were published in Nature Communications (doi:10.1038/ncomms6863; published online 18 December 2014). “Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI [myocardial infarction],” write the authors of the report, led by Maria Blasco (Spanish National Cancer Research Centre, Madrid).

Telomerase is normally expressed during embryonic development but silenced after birth. The researchers used an adenovirus vector to activate telomerase expression specifically in the hearts of adult mice and then, 2–3 weeks later, when telomerase expression was maximal, induced myocardial infarction by ligation of the coronary artery. Telomerase expression improved mouse survival after infarction: more than 74% of mice expressing telomerase survived compared with only 57% of control mice. Telomerase expression also preserved the myocardium, improved ventricular function and increased metabolic activity and tissue remodeling while minimizing infarct size and scar formation. Furthermore, mice expressing telomerase showed greater telomere length among cardiomyocytes and larger numbers of cycling cardiomyocytes. Activation of telomerase was also associated with changes in gene expression reflecting the activation of cardioprotective pathways. Gene expression profiles of adult mice with activated telomerase resembled those of neonatal mice, in which telomerase is normally active and cardiac regeneration can occur.

Taken together, the results suggest that telomerase expression might trigger heart muscle regeneration, a key therapeutic objective for myocardial infarction as well as chronic heart failure and other forms of cardiovascular disease. “Although efficient heart regeneration has been one of the goals of cardiology for the treatment of MI [myocardial infarction] and prevention of heart failure, no significant advances have been made in this regard,” the authors wrote.

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The authors conclude that “telomerase activation in the adult heart is beneficial for survival in the murine model after acute MI [myocardial infarction], which is coincidental with longer telomeres and activation of several pathways associated with cardiac protection and regeneration. These findings serve as proof of concept for the development of innovative strategies based on telomerase activation to treat chronic and acute heart failure.”

According to a press release, Blasco and her collaborators next plan to test the effects of telomerase activation in pigs, a larger animal model whose cardiac anatomy and function more closely resemble those of humans.