Abstract
Unlike some lower vertebrates which can completely regenerate their heart, the human heart is a terminally differentiated organ. Cardiomyocytes lost during cardiac injury and heart failure cannot be replaced due to their limited proliferative capacity. Therefore, cardiac injury generally leads to progressive failure. Here, we summarize the latest progress in research on methods to induce cardiomyocyte cell cycle entry and heart repair through the alteration of cardiomyocyte plasticity, which is emerging as an effective strategy to compensate for the loss of functional cardiomyocytes and improve the impaired heart functions.
Highlights
Heart failure is the most prominent cause of hospitalization and one of the leading causes of mortality globally
Katrina et al used a combination of cyclin B1 and constitutively active cell division cycle 2 kinase (CDC2AF) to induce cell cycling in fetal, neonatal, and adult cardiomyocytes isolated from Wistar rats and showed a significant increase in the number of tropomyosin-positive cells [34]
Mohamed et al showed efficient induction of stable cell cycle division, assessed by EdU and phospho-histone H3 (PHH3), in 15–20% of adult mouse, rat, and hiPS cardiomyocytes overexpressing a combination of four cell cycle genes; cyclin-dependent kinase 1 (CDK1), CDK4, cyclin B1, and cyclin D1
Summary
Heart failure is the most prominent cause of hospitalization and one of the leading causes of mortality globally. Katrina et al used a combination of cyclin B1 and constitutively active cell division cycle 2 kinase (CDC2AF) to induce cell cycling in fetal, neonatal, and adult cardiomyocytes isolated from Wistar rats and showed a significant increase in the number of tropomyosin-positive cells [34]. Mohamed et al showed efficient induction of stable cell cycle division, assessed by EdU and PHH3, in 15–20% of adult mouse, rat, and hiPS cardiomyocytes overexpressing a combination of four cell cycle genes; cyclin-dependent kinase 1 (CDK1), CDK4, cyclin B1, and cyclin D1 (termed 4F). Sirt-1 overexpression showed a significant reduction in active P21 acetylation, which resulted in a release of the inhibitory effect on the cell cycle genes and a significant increase in the mitotic markers, including PHH3 and Aurora B kinase-positive nuclei [37]. Engel et al have shown that cardiac-specific P38α knockout mice exhibited an increase in cardiomyocyte mitosis, indicated by increased BrdU and pHH3-positive nuclei, and that this was associated with an increase in the cell counts in vitro and in vivo [24]
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