Abstract:
Current treatments for myocardial damage following a heart attack are insufficient and the mortality rate is around 40%. Previous work has assessed the effectiveness of bone marrow mononuclear cell (MNC) therapy in an ischemia reperfusion rat model and shown that MNCs home in on the infarct area leading to smaller infarct size and improved cardiac function as measured by fractional shortening. The mechanism by which MNCs trigger growth of new cardiomyocytes are not known. Our aim was to discover which proteins and pathways are triggered by MNC treatment using comparative protein profiling by 2DE and LC/MS/MS. Three groups of animals were compared; two groups had the left anterior descending coronary artery ligated for 30 minutes followed by reperfusion for 6 hours, one group then received MNC preparation post reperfusion the other group had no treatment . The third group underwent a sham operation (all groups n=3). Approximately 1100 spots were included in the analysis, 69 of these differed significantly (p≤0.05) between the groups by ≥3 fold. Of these proteins, 13 were altered after MI and were also affected by treatment such that spot intensity return to levels similar to the sham group. The groups identified include energy metabolism and structural proteins as well as a key member of apoptosis regulation. To complement this analysis, gene expression profiling was also performed on the same samples using Illumina expression chips (RatRaf-12) with ~21,000 genes assessed; preliminary analyses of this data reveal no significantly differentially expressed genes between groups suggesting the physiological changes are all driven by post-translational processes.
