Damaged heart repair mechanisms identified
Heart disease is the number one cause of death and disability in many European countries. The EU-funded CARDIOGEN (The molecular mechanisms of heart regeneration) study specifically investigated regeneration of heart muscle, the myocardium, a controversial issue in heart research circles. Previously thought to be derived from stem/progenitor cells, CARDIOGEN researchers uncovered the molecular mechanisms at work when myocardium regenerates from existing cardiomycetes after cardiac insult. Significantly, other research has shown that neonatal mice regenerate heart muscle from cardiomycetes, suggesting that mammals have this potential. The CARDIOGEN team identified a number of genes and processes necessary for successful heart development and regeneration. Fish expressing a dominant negative form of gene A had severely disrupted heart regeneration indicating this gene A plays a critical role in the process. Work on macrophages unveiled a gene that breaks down scar tissue associated with cardiac injury. The researchers hope to identify differences in macrophage response in adult mammals to target this population of cells for future therapeutic solutions. During cardiogenesis, researchers discovered that gene Y, a functional mechanosensitive ion channel responds to haemodynamic forces in the heart by triggering the release of nitric oxide in the outflow tract. Analysis of exomic data from patients who suffer from bicuspid valve disease revealed that deleterious mutations in this gene are associated with this condition. Identification of genes and processes involved in heart regeneration in zebrafish means future translation into equivalent processes in mammals and ultimately humans. CARDIOGEN data on mutations leading to coronary heart disease can be incorporated into clinical diagnostics for rapid interventions and new therapeutic targets.
