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The Transcriptome Responses of Cardiomyocyte Exposed to Hypothermia

ABSTRACT: Hypothermia affects the body in positive and negative consequences. In cardiac, hypothermia depresses myocardial contraction, slows conduction, and decreases metabolic rate. However, little is known about the molecular mechanism. Here we compare the genes expression of human adult ventricular cardiomyocyte cells (AC16) treated with hypothermia, trying to find changes under different temperatures and then elucidate the candidate genes that may play important roles in the response to hypothermia. A total of 2413 differentially expressed genes (DEGs) were identified by microarray hybridization, which provided abundant data for further analysis. Gene Ontology enrichment analysis revealed that genes related to gene transcriptions, protein and lipid metabolic were significantly enriched. KEGG analysis showed that DEGs were significantly enriched in TGF-β pathway and cytokine-cytokine receptor interaction, which may play important roles in response to hypothermia. A set of TFs (CPBP, Churchill, NF-AT1, GKLF, SRY, ZNF333, ING4, myogenin, DRI1 and CRX) was recognized to be the functional layer of key nodes, which mapped the signal of hypothermia to transcriptome. These identified DEGs, pathways and predicted TF could facilitate further investigations of the detailed molecular mechanisms, making it possible to take advantage of the potential applications of hypothermia in broader ranger

ORGANISM(S): Homo sapiens

PROVIDER: GSE71361 | GEO | 2015/07/28

SECONDARY ACCESSION(S): PRJNA291040

REPOSITORIES: GEO

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Project description:Background: Moderate hypothermia (32oC for 12 – 72 hours) has therapeutic applications, but the mechanisms by which it affects cellular function are unclear. We tested the hypothesis that moderate hypothermia produces broad changes in gene expression by human cells at the level of mRNA. Methods: Acute monocytic leukemia THP-1 cells were incubated under control conditions (37oC) or moderate hypothermia (32oC) for 24 hours. Cellular mRNA was extracted and a cold stress response was confirmed by examining the expression of the cold-inducible gene CIRBP by reverse transcription PCR (RT-PCR). Gene expression analysis was performed on seven sets of samples with Affymetrix U133A chips, using established statistical methods. Sequences were considered to be affected by cold if they showed statistically significant changes in expression and also met published post-hoc filter criteria (changes in geometric mean expression of 2-fold or greater and detection calls of “present” or “marginal” in at least half of the experiments). The changes in expression of a select number of these sequences were further confirmed by PCR. Results: 167 sequences met our prospectively defined criteria for a change in expression; 67 showed increases in expression and 100 showed decreases in expression. Consistent with prior literature, the cold-inducible genes CIRBP and RBM3 showed increases in expression. Functional categories affected by cold stress included genes involved in immune responses, cell growth, proliferation, and differentiation, and metabolism and biosynthesis. Several heat shock proteins (HSPs) showed decreases in expression. Conclusions: Moderate hypothermia produces substantial changes in cellular gene expression, in categories potentially of importance to systemic function. Interestingly, cold exposure without re-warming decreased the expression of several HSPs. Our in vitro findings suggest that moderate hypothermia in vivo might produce physiologically important changes in gene expression by circulating leukocytes. Keywords: Stress response / hypothermia

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The Transcriptome Responses of Cardiomyocyte Exposed to Hypothermia

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