Soren Paludan Sheikh is the Department Head for Clinical Biochemistry and Pharmacology at Danish Centre for Regenerative Medicine in Denmark.
Abstract
Myocardial infarction in mammals is generally considered to result in scar formation, whereas zebrafish completely regenerate their hearts following an intermediate and reversible state of fibrosis after apex resection (AR). Recently, using the AR procedure, seven day old mice were suggested to have full capacity for cardiac regeneration. In contrary, using the same mouse model others have shown that the regeneration process is incomplete and that scarring still remains 21 days after AR. The present study tested the hypothesis that like in zebrafish fibrosis in neonatal mammals could be an intermediate response before the onset of complete heart regeneration. Myocardial damage or sham surgery was performed by AR in postnatal day 1 mice and myocardial function and scarring assessed at day 180 using 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (FDG-PET) and histology, respectively. AR mice exhibited decreased ejection fraction and wall motion but increased end-diastolic and systolic volumes. Scarring with collagen accumulation was still substantial, and the heart size enlarged, yet cardiomyocyte size was unaffected. Similar data were obtained for rats at an early time point. It can be concluded that the data underscore that fibrosis following apex resection is irreversible and that this scar likely contributes to AR mice developing dilated cardiomyopathy.
