BACKGROUND: In embryonic myocytes, closure of the mitochondrial permeability transition pore (PTP) drives mitochondrial maturation and cardiac myocyte differentiation. Since neonatal cardiac myocytes remain relatively immature, we hypothesized that inducing PTP closure at this age, by inhibiting the PTP regulator, @entity26579 ( @entity26579 ), genetically or with @entity205 ( @entity9472 ) and @entity20200 , would increase cardiac function by increasing mitochondrial maturation and myocyte differentiation. METHODS: Cultured neonatal myocytes or neonatal @entity19 were treated for 5 days with vehicle, @entity9472 or @entity20200 . Mitochondrial function and structure were measured in vitro. Myocyte differentiation was assessed by immunolabeling for contractile proteins. Cardiac function was determined using echocardiography. RESULTS: The probability of PTP opening was high in WT neonatal myocytes. Treatment with @entity9472 or @entity20200 in vitro increased mitochondrial structural complexity and membrane potential, decreased reactive @entity26 species levels, and increased myocyte differentiation. WT @entity19 treated with either @entity9472 or @entity20200 in vivo for the first 5 days of life had higher ejection fractions. Deleting @entity26579 had similar effects as @entity9472 and @entity20200 on all parameters. CONCLUSIONS: It may be feasible to inhibit the PTP using available drugs to increase mitochondrial maturation, myocyte differentiation, and cardiac function in neonates.Pediatric Research (2017); doi:10.1038/pr.2017.19.

Preventing Permeability Transition Pore Opening Increases Mitochondrial Maturation, Myocyte Differentiation and Cardiac Function in the Neonatal XXXX Heart.

@entity9472 :: ('D016572', 'Chemical') :: ['CsA'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity20200 :: ('MESH:C090438', 'Chemical') :: ['NIM811'] @entity26579 :: ('105675(Tax:10090)', 'Gene') :: ['CyPD', 'cyclophilin D'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['Cyclosporin A']
@entity19 :: (10090,Species) :: ['Mouse']
