Key result
Pre-conditioning with CpG 1668 in mice induced up-regulation of protective pathways and suppression of proinflammatory activity 24 hours post-myocardial ischaemia/reperfusion injury.
Why the study?
Does pre-conditioning with CpG ODN 1668 alter gene expression profiles to ameliorate myocardial ischaemia/reperfusion injury in C57BL/6 mice?
Does pre-conditioning with CpG ODN 1668 alter gene expression profiles to ameliorate myocardial ischaemia/reperfusion injury in C57BL/6 mice?
Pre-conditioning with CpG ODN 1668 induces a cardioprotective genetic profile characterized by up-regulation of cellular integrity pathways and suppression of inflammation in a murine model of myocardial ischemia/reperfusion injury.
Hypothesis-generating for CpG preconditioning in murine I/R injury; leaves open translational relevance to human myocardial ischaemia/reperfusion.
We previously demonstrated that pre-conditioning with CpG oligonucleotide (ODN) 1668 induces quick up-regulation of gene expression 3 hours post-murine myocardial ischaemia/reperfusion (I/R) injury, terminating inflammatory processes that sustain I/R injury. Now, performing comprehensive microarray and biocomputational analyses, we sought to further enlighten the "black box" beyond these first 3 hours. C57BL/6 mice were pretreated with either CpG 1668 or with control ODN 1612, respectively. Sixteen hours later, myocardial ischaemia was induced for 1 hour in a closed-chest model, followed by reperfusion for 24 hours. RNA was extracted from hearts, and labelled cDNA was hybridized to gene microarrays. Data analysis was performed with BRB ArrayTools and Ingenuity Pathway Analysis. Functional groups mediating restoration of cellular integrity were among the top up-regulated categories. Genes known to influence cardiomyocyte survival were strongly induced 24 hours post-I/R. In contrast, proinflammatory pathways were down-regulated. Interleukin-10, an upstream regulator, suppressed specifically selected proinflammatory target genes at 24 hours compared to 3 hours post-I/R. The IL1 complex is supposed to be one regulator of a network increasing cardiovascular angiogenesis. The up-regulation of numerous protective pathways and the suppression of proinflammatory activity are supposed to be the genetic correlate of the cardioprotective effects of CpG 1668 pre-conditioning.
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Hilbert et al. (2018) studied Myocardial ischaemia/reperfusion injury. CpG oligonucleotide (ODN) 1668 pre-conditioning vs. Control ODN 1612 was evaluated on Gene expression profile (microarray analysis) 24 hours post-I/R. Pre-conditioning with CpG 1668 in mice induced up-regulation of protective pathways and suppression of proinflammatory activity 24 hours post-myocardial ischaemia/reperfusion injury.
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