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Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion.


ABSTRACT: Aims:Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesized that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury. Methods and results:Mice were created over-expressing the sarcomeric MtCK gene with ?MHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates. MtCK activity was 27% higher than WT, with no change in other CK isoenzymes or creatine levels. Electron microscopy confirmed normal mitochondrial cell density and mitochondrial localization of transgenic protein. Respiration in isolated mitochondria was unaltered and metabolomic analysis by 1?H-NMR suggests that cellular metabolism was not grossly affected by transgene expression. There were no significant differences in cardiac structure or function under baseline conditions by cine-MRI or LV haemodynamics. In Langendorff-perfused hearts subjected to 20?min ischaemia and 30?min reperfusion, MtCK-OE exhibited less ischaemic contracture, and improved functional recovery (Rate pressure product 58% above WT; P?

SUBMITTER: Whittington HJ 

PROVIDER: S-EPMC5909653 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion.

Whittington Hannah J HJ   Ostrowski Philip J PJ   McAndrew Debra J DJ   Cao Fang F   Shaw Andrew A   Eykyn Thomas R TR   Lake Hannah A HA   Tyler Jack J   Schneider Jurgen E JE   Neubauer Stefan S   Zervou Sevasti S   Lygate Craig A CA  

Cardiovascular research 20180501 6


<h4>Aims</h4>Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesized that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury.<h4>Methods and results</h4>Mice were created over-expressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) litt  ...[more]

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