Abstract 16531: Acute Hyperglycemia Polarizes and Myocardial Infarction Amplifies Differential Profiles of Gene Expression in Circulating Leukocytes
Introduction: Acute hyperglycemia during MI is associated with higher clinical mortality and increased infarct size in the mouse model of reperfused MI. We used microarray analysis to compare gene expression in leukocytes isolated from normal and hyperglycemic mice after sham surgery or reperfused MI.
Methods: Four treatment groups of n=4, 12 wk male C57Bl/6 mice were studied: euglycemic sham (EuSS) & hyperglycemic sham (HySS) surgery, and euglycemic MI(EuMI) & hyperglycemic MI (HyMI). Hyperglycemia was induced by 20% dextrose (10mL/kg) IP 20 min prior to MI. MI consisted of 30 min coronary occlusion with 2 h of reperfusion, after which mRNA was isolated from whole blood. Gene profiling was done on Illumina BeadChips using the iScan system. To verify expression patterns, 8 differentially-expressed genes were analyzed by qPCR (n=3/group).
Results: Differences in gene expression were detected between EuSS, HySS & EuMI mice, but none of these comparisons reached significance (all FDR ≥ 0.47). However, the EuMI vs HyMI comparison revealed a significant number of genes that were differentially regulated (241 with FDR < 0.05). Differences between EuSS & HySS expression were amplified (and became significant) only after MI (i.e., in the comparison between EuMI & HyMI mice: Panel A). The 8 genes analyzed by qPCR were found to have a correlation of R2=0.94 with BeadChip fold change data. These genes also exemplified the pattern of gene expression under hyperglycemic conditions that became more pronounced following MI (Panel B). HEFalMp network analysis identified genes from the set of 241 with FDR < 0.05 involved in regulation of T cell activation & differentiation, calcium ion homeostasis, and signal transduction (p < 0.05 for all).
Conclusions: Hyperglycemia imparts changes in the patterns of gene expression that are amplified by MI. This altered immune response may underlie the larger infarcts in hyperglycemic mice and may contribute to higher mortality in patients with MI.
Author Disclosures: R.S. Smith: None. B.A. Piras: None. C.R. Farber: None. Z. Yang: None. I.L. Kron: None. B.A. French: Research Grant; Significant; From AstraZeneca.
- © 2015 by American Heart Association, Inc.