DNA Microarray Analysis of Hypothermic Murine Myocardium to Study Pathophysiology and Identify Forensic Biomarkers

We used DNA microarray technology to analyze the myocardial transcriptome of mice killed via experimentally induced hypothermia. This analysis identified significant differential regulation of 3438 genes; specifically, 1704 genes were upregulated, and 1734 were downregulated in response to hypothermia. The gene encoding granzyme A was the most upregulated gene, and that encoding solute carrier family 41 member 3 was the most downregulated. Gene-set analysis identified significant hypothermia-induced variation in 79 pathways, and we suggest that pathways related to granzyme A and cell death may be involved in cardiac pathogenesis of hypothermia. Gene-function-category analysis demonstrated the most highly represented categories among the upregulated and downregulated genes were cellular process (biological process), binding (molecular function), and cell and cell part (cellular component). The presented findings clearly demonstrated that acute myocardial responses to hypothermia did occur; they also indicated several cardiac-related candidate genes as forensic biomarkers of hypothermia. Hypothermia-induced myocardial cell death would be an irreversible change that, we believe, may explain the circulatory failure, resistance to treatment, and high mortality associated with hypothermia. Furthermore, the present microarray data may facilitate development of immunohistochemical analysis and protocols to be used for human forensics and may be beneficial in clinical research on hypothermia.