Identification of candidate genes and pathways in limonin-mediated cardiac repair after myocardial infarction

Abstract

Background: Myocardial infarction (MI) resulting from acute coronary ischemia may cause significant morbidity and mortality, and microRNAs play a vital role in this pathophysiology. Limonin (LIM) is a natural medicine from citrus fruit that protects organs against ischemic diseases, but the candidate genes and pathways associated with cardioprotection are unknown. Methods: MI was induced by ligating the left anterior descending coronary in male Sprague-Dawley rats. LIM was orally administered for 7 days after the induction of MI. Subsequently, the hearts were collected to examine significant changes in microRNAs and mRNAs among the control (CON), MI, and LIM + MI groups. Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction (PPI) networks were used to identify the biological functions and signaling pathways of differentially expressed mRNAs. Candidate genes were validated by RT-qPCR. Results: Compared to the CON group, MI caused significant changes in the expression of 26 microRNAs and 1979 mRNAs. The bioinformatics analysis showed that inflammation, apoptosis, and oxidation were enriched in GO terms, while RAP1, PI3K/AKT, RAS, and cGMP-PKG were enriched in KEGG pathways. In addition, compared to the MI group, LIM induced significant changes in the expression of 4 microRNAs and 173 mRNAs. The differentially expressed mRNAs were related to collagen biosynthesis, the immune response, extrinsic apoptosis, and tight junctions. One microRNA (rno-miR-10a-5p) and 2 mRNAs (IGLON5 and LMX1A) were differentially expressed among the CON, MI, and LIM + MI groups. Conclusions: Our results suggest that the rno-miR-10a-5p-IGLON5/LMX1A axis may be a candidate pathway and promising target through which LIM alleviates MI-induced cardiac dysfunction.

Keywords

• Myocardial infarction
• Limonin
• MicroRNA
• mRNA