The mitochondrial permeability transition pore plays a central role in cardioprotection: an investigation using the cyclophilin D knockout mice. (360G-Wellcome-081285_Z_06_Z)

£144,844

Novel interventions are required to protect the myocardium against ischaemia-reperfusion injury. In this regard the cardioprotective interventions of ischaemic preconditioning (IPC) and ischaemic postconditioning (IPost), which describe the application of brief episodes of sub-lethal ischaemia either prior to the lethal ischaemic insult or at the time of reperfusion respectively, limit myocardial infarction. Studies suggest that the mitochondrial permeability transition pore (mPTP), a non-specif ic pore of the inner mitochondrial membrane, which is believed to open in the early minutes of reperfusion, is central to the cardioprotection induced by IPC, IPost and several pharmacological cardioprotective agents. Previous studies investigating the role of the mPTP have relied on pharmacological manipulation, however in the present proposal we are able, for the first time, to study the role of the mPTP in ischaemic and pharmacological preconditioning and postconditioning using a transgenic m odel in which cyclophilin-D has been genetically knocked out and therefore unable to form a functional mPTP. We will examine the cardioprotective interventions of ischaemic and pharmacological preconditioning and postconditioning in this animal, using an in vivo model of myocardial ischaemia-reperfusion injury in order to assess the role of the mPTP and its interaction with the survival kinases (Akt and Erk1/2) in these settings.

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Grant Details

Amount Awarded 144844
Applicant Surname Yellon
Approval Committee Physiological Sciences Funding Committee
Award Date 2007-02-22T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Project Grant
Internal ID 081285/Z/06/Z
Lead Applicant Prof Derek Yellon
Partnership Value 144844
Planned Dates: End Date 2010-03-31T00:00:00+00:00
Planned Dates: Start Date 2007-04-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London