MiRNA Expression Profile of the Myocardial Tissue of Pigs With Coronary Microembolization

Cell Physiol Biochem. 2017;43(3):1012-1024. doi: 10.1159/000481699. Epub 2017 Oct 2.

Abstract

Background/aims: Coronary microembolization (CME) is a serious complication of coronary heart disease and is considered as a strong predictor of poor long-term prognosis and major cardiac adverse events. Here, we identified differentially expressed microRNAs (miRNAs) in the myocardial tissue of CME pigs, and predicted and analyzed the possible functions of their target genes.

Methods: Twelve Bama mini-pigs were randomly assigned to the sham and CME group (n = 6 in each group). The two groups were compared with regard to heart function, area of infarction, cardiomyocyte apoptosis, and myocardial expression of TNF-α, IL-1β and IL-6. Further, miRNA chip analysis was used to screen for differentially expressed miRNAs, and the results were validated by real-time PCR. Bioinformatics methods were used to predict and analyze the functions of the target genes of the identified miRNAs.

Results: The model CME pigs showed significantly increased expression of TNF-α, IL-1β and IL-6, as well as micro-infarction lesions and cell apoptosis in the myocardial tissue. Thus, the model was established successfully. In the myocardial tissue of the CME pigs, the expression of ssc-miR-92b-5p, ssc-miR-491, ssc-miR-874, ssc-miR-425-3p, ssc-miR-376a-5p, ssc-miR-370, ssc-miR-30c-3p, ssc-miR-493-5p and ssc-miR-323 was significantly increased, whereas the expression of ssc-miR-136 and ssc-miR-142-3p was significantly decreased. GO and KEGG pathway analysis indicated that the target genes of these miRNAs are mainly associated with cell proliferation, apoptosis, necrosis, inflammation, and fibrosis.

Conclusion: The differentially expressed miRNAs identified in the myocardial tissue of CME pigs could be new biomarkers or potential treatment targets for CME.

Keywords: Coronary microembolization; Gene expression profile; MiRNA; Myocardial damage.

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Cluster Analysis
  • Disease Models, Animal
  • Female
  • Heart Ventricles / physiopathology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Swine
  • Swine, Miniature
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Interleukin-1beta
  • Interleukin-6
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Caspase 3