Background <p>The molecular mechanisms of inflammatory pathophysiology after intracerebral hemorrhage (ICH) are not well established. We report mRNA-seq and miRNA-seq in the peripheral blood of ICH patients with three serial samples during the first week after the stroke.</p> Methods <p>Twenty-seven ICH patients were enrolled via 24/7 screening and peripheral blood sampled at &lt; 24&#xa0;h (baseline), 72&#xa0;h (+/-12&#xa0;h), and 7 days (+/- 2 days) from last known normal. mRNA-seq and miRNA-seq were assessed for differential expression (DE) between the time point comparisons. Pathways identified via enrichment analysis (STRING, Reactome, Ingenuity Pathway Analysis) were tested via paired t-test and principal component analysis (PCA). Correlations between miRNA/mRNA pairs were computed.</p> Results <p>For DE mRNA at 72&#xa0;h vs. baseline, the main enriched pathways pertained to neuronal function and synaptic transmission; prominent neuron-related genes from these pathways are also implicated in platelet activation. For 7 days vs. baseline, neutrophil degranulation and ribosomal biogenesis were the most enriched pathways; PCA also suggested neutrophil degranulation was the pathway most significantly different at 7 days vs. baseline compared with 72&#xa0;h vs. baseline (<i>p</i> = 0.02). miR-3613 and miR-3690 had decreased expression at 7 days and were the miRNA most correlated with DE genes from the neutrophil degranulation pathway.</p> Conclusion <p>Neutrophil degranulation was the prominent enriched pathway at 7 days after ICH and correlated with decreased miR-3613 and miR-3690. Further research is warranted of neutrophils in post-ICH inflammatory pathophysiology and functional validation studies of miR-3613 and miR-3690 as potential regulators of neutrophil degranulation after ICH.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Neutrophil degranulation is increased at seven days after human intracerebral hemorrhage, but not at 72 h, and correlates with decreased miR-3613 and miR-3690

  • Kyle B. Walsh,
  • Miranda C. Marion,
  • Dengfeng Li,
  • Hannah C. Ainsworth,
  • Amy Zinnia,
  • Xiang Zhang,
  • Stacie L. Demel,
  • Brady Williamson,
  • David J. Roh,
  • Robert Campbell,
  • Frederik Denorme,
  • Daniel Woo,
  • Carl D. Langefeld

摘要

Background

The molecular mechanisms of inflammatory pathophysiology after intracerebral hemorrhage (ICH) are not well established. We report mRNA-seq and miRNA-seq in the peripheral blood of ICH patients with three serial samples during the first week after the stroke.

Methods

Twenty-seven ICH patients were enrolled via 24/7 screening and peripheral blood sampled at < 24 h (baseline), 72 h (+/-12 h), and 7 days (+/- 2 days) from last known normal. mRNA-seq and miRNA-seq were assessed for differential expression (DE) between the time point comparisons. Pathways identified via enrichment analysis (STRING, Reactome, Ingenuity Pathway Analysis) were tested via paired t-test and principal component analysis (PCA). Correlations between miRNA/mRNA pairs were computed.

Results

For DE mRNA at 72 h vs. baseline, the main enriched pathways pertained to neuronal function and synaptic transmission; prominent neuron-related genes from these pathways are also implicated in platelet activation. For 7 days vs. baseline, neutrophil degranulation and ribosomal biogenesis were the most enriched pathways; PCA also suggested neutrophil degranulation was the pathway most significantly different at 7 days vs. baseline compared with 72 h vs. baseline (p = 0.02). miR-3613 and miR-3690 had decreased expression at 7 days and were the miRNA most correlated with DE genes from the neutrophil degranulation pathway.

Conclusion

Neutrophil degranulation was the prominent enriched pathway at 7 days after ICH and correlated with decreased miR-3613 and miR-3690. Further research is warranted of neutrophils in post-ICH inflammatory pathophysiology and functional validation studies of miR-3613 and miR-3690 as potential regulators of neutrophil degranulation after ICH.