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Purpose of Review The typical remodeling process after cardiac injury is scarring and compensatory hypertrophy. The limited regeneration potential of the adult heart is thought to be due to the post-mitotic status of postnatal cardiomyocytes, which are mostly binucleated and/or polyploid. Nevertheless, there is evidence for cardiomyocyte turnover in the adult heart. The purpose of this review is to describe the recent findings regarding the proliferative potential of mononuclear cardiomyocytes and to evaluate their function in cardiac turnover and disease. Recent Findings There is overwhelming evidence from carbon-dating in humans and multi-isotope imaging mass spectrometry in mice that there is a very low but detectable level of turnover of cardiomyocytes in the heart. The source of this renewal is not clear, but recent evidence points to a population of mononuclear, diploid cardiomyocytes that are still capable of authentic cell division. Controversy arises when their role in cardiac repair is considered, as some studies claim that they contribute to repair by cell division while other studies do not find evidence for hyperplasia but hypertrophy. Stimulation of the mononuclear cardiomyocyte population has been proposed as a therapeutic strategy in cardiac disease. Summary The studies reviewed here agree on the existence of a low annual cardiomyocyte turnover rate which can be attributed to the proliferation of mononuclear cardiomyocytes. Potential roles of mononucleated cardiomyocytes in cardiac repair after injury are discussed.

Despite the great progress on the cell biology of programmed cell death (PCD), its incidence and exact time course during embryonic and particular heart development are still unclear. This is also due to the lack of models enabling to directly identify and monitor PCD cells at different time points in vivo. Herein we report generation of transgenic murine embryonic stem cell and mouse models expressing secreted Annexin V-YFP under control of the CAG promoter. This enables to visualize and quantify PCD in vitro and in vivo during embryonic development. At early embryonic stages we found Annexin V-YFP+ fluorescent cells in known areas of PCD, such as the otic ring and at the site of neural tube closing, underscoring its specificity for detection of PCD. We have focused our detailed analysis primarily on PCD in the embryonic heart for a better understanding of its role during development. Our findings reveal that PCD peaks at early stages of cardiogenesis (E9.5–E13.5) and strongly decreases thereafter. Moreover, the PCD cells in the heart are predominantly cardiomyocytes, and an unexpected area of prominent cardiac PCD are the ventricular trabeculae (E9.5–E14.5). Thus, the sA5-YFP mouse line provides novel insight into the incidence and relevance of cardiac PCD during embryonic development ex- and in vivo.