The Role of miR-208 in the Molecular Mechanism of Post-operative Atrial Fibrillation. (360G-Wellcome-100023_Z_12_Z)
Post-operative atrial fibrillation (POAF) is the commonest complication after cardiac surgery and may be life-threatening. Currently, it is not possible to identify patients at increased risk of AF. MicroRNAs (miRNA) are inhibitory regulators of mRNA and may act as biomarkers of cardiovascular disease. My preliminary work has identified 16 miRNAs differentially expressed within atrial cardiomyocytes that characterise patients at risk of AF intra- operatively, 2-3 days before its onset. Ba sed on this pilot data I propose the following 3-part study: 1. A prospective Cohort study of human patients undergoing coronary surgery to identify the differential expression of miRNA in POAF. 2. Determining the effect of up-regulation of miR-208 in a Kir2.1 mouse model of POAF and its role as a potential therapeutic target. 3. Investigating changes in mir-208 target proteins known to play a role in electrical remodelling and cardiomyocte energy substrate provision (SK3 and THRAP1). Key Goals: 1. To characterize the unique miRNA signature of POAF in humans and develop a novel serum biomarker to predict POAF. 2. To verify these miRNA changes in a mouse model (Kir2.1) of POAF 3. To determine whether miR-208 regulation of the target proteins SK3 and THRAP1 plays a role in POAF pathogenesis.
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Grant Details
| Region | London |
| Award Date | 2012-11-20T00:00:00+00:00 |
| Sponsor(s) | Lord Ara Darzi |
| Internal ID | 100023/Z/12/Z |
| Planned Dates: End Date | 2016-03-31T00:00:00+00:00 |
| Planned Dates: Start Date | 2013-04-01T00:00:00+00:00 |
| Amount Awarded | 186446 |
| Financial Year | 2012/13 |
| Lead Applicant | Miss Leanne Harling |
| Grant Programme: Title | Research Training Fellowship |
| Applicant Surname | Harling |
| Approval Committee | Clinical Interview Committee |
| Recipient Org: Country | United Kingdom |
| Recipient Org: City | London |
| Has the grant transferred? | No |
| Research conducted at multiple locations? | No |
| Total amount including partnership funding | 186446 |