Abstract 17459: Acute Hyperglycemia Synergizes with Myocardial Infarction to Induce Significant Changes in Leukocyte Gene Expression Profiles
Introduction: Acute hyperglycemia during myocardial infarction (MI) is associated with higher clinical mortality and increased infarct size in the mouse model of reperfused MI. The mechanisms behind this are poorly understood, but may involve activation of circulating immune cells. Using gene profiling methods, we compared whole-genome gene expression in peripheral blood leukocytes isolated from normal and hyperglycemic mice after reperfused MI or sham surgery.
Methods: Four treatment groups of n=4, male, 12 wk C57Bl/6 mice were studied: euglycemic & hyperglycemic sham surgery, and euglycemic & hyperglycemic MI. MI consisted of 30 min coronary occlusion followed by 2 h reperfusion. Hyperglycemia was induced by 20% dextrose IP (10mL/kg) 20 min prior to coronary occlusion. After 2 h of reperfusion, mRNA was isolated from whole blood. Gene profiling was performed on Illumina BeadChips with the iScan system. Differentially expressed genes with greater than 30% fold-change were used to perform network analysis using HEFalMp software.
Results: No genes with significant (FDR < 0.05) differential gene expression were found in peripheral blood leukocytes between euglycemic MI vs. euglycemic sham mice nor between euglycemic sham vs. hyperglycemic sham mice. However, between euglycemic MI vs. hyperglycemic MI mice, a significant number of genes were differentially regulated (246 with FDR < 0.05). Network analysis with HEFalMp identified a large number of genes involved in immune system functions, including: regulation of T cell activation (p < 0.001), T cell differentiation (p < 0.001), calcium ion homeostasis (p < 0.001) and signal transduction (p = 0.03) (Table 1).
Conclusions: This is the first gene profiling study to show that leukocyte gene expression is significantly altered by acute hyperglycemia during MI. This altered immune response may underlie the larger infarct size seen in hyperglycemic mice, and may contribute to the higher mortality seen in human patients.
- © 2010 by American Heart Association, Inc.