Redox Regulation of Cardiomyocyte Renewal

European Coordinator:
  • Miguel TORRES, Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.) (CNIC), Madrid (Spain)
North American Coordinator:
  • Hesham A. SADEK, University of Texas Southwestern Medical Center, Dallas, TX (USA)
Members:
  • Bertrand FRIGUET, Université Pierre et Marie Curie, Paris (France)
  • Jonas FRISEN, Karolinska Institutet, Stockholm (Sweden)
  • Roger HAJJAR, Icahn School of Medicine at Mount Sinai, New York (USA)
  • Ajay SHAH, King’s College London (UK)
  • Luke SZWEDA, University of Texas Southwestern Medical Center, Dallas, TX (USA)
  • Magdi YACOUB, The Magdi Yacoub Institute, London (UK)

Many animals are able to regenerate heart muscle in the face of injury, growing new cells from residual heart cells. Adult mammals, including humans, lack this capacity to regenerate the heart; in the face of injury to the heart, such as from disease of the arteries of the heart, heart failure develops. It appears, however, that in at least some mammals, newborns have the ability to grow new heart cells, but lose this ability soon after birth. This TNE has been organized to examine how this ability is lost, and whether it can be recovered in adults to grow new heart cells if the heart is injured by disease. The investigators of this network are focusing on the signals in the environment of the newborn heart which subsequently lead to the loss of the heart cell’s ability to reproduce soon after the neonatal period. They believe that these signals arise from a change in the chemical environment of the heart, resulting from the metabolic changes in the newborn as it breathes on its own and consumes oxygen. One of the consequences of consuming oxygen to create energy is the creation of reactive oxygen species (ROS), which can damage DNA. Network investigators believe that ROS serve as the signal to limit the ability of the heart cell to reproduce. They plan to clarify the mechanisms of this link between ROS, DNA damage, and the ability to regenerate heart cells. They will also explore how they might use this knowledge to improve cardiac regeneration and overall heart function in the case of human cardiovascular disease.