Cardiomyocyte proliferation: remove brakes and push accelerators

Abstract

Adult mammalian hearts cannot repair by themselves after injury due to limited proliferation of cardiomyocytes; removal of cell cycle blocker and/or addition of drugs that boost proliferation of cardiomyocytes provide potential means to cardiac regeneration. Three publications that appeared recently in Nature and Cell Research now provide new hope to the treatment of heart injuries.

Figure 1

Signaling pathways governing cardiomyocyte proliferation. Left: YAP phosphorylated by Hippo signaling is sequestered by DGC. Myofiber is mature with intact sarcomeric structure. PPARδ/PDK1/AKT/GSK3β/β-cat activity is maintained at basal level. Right: ECM protein agrin binds DGC, which promotes the disassembly of DGC and subsequently myofiber disassembly and YAP activation^,. Chemical compound carbacyclin increases PPARδ activity, which activates β-cat via PDK1/AKT/GSK3β pathway. YAP-TEAD and β-cat-TCF promote transcriptional regulation of cardiomyocyte proliferation.