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Dynamic Proteomic and miRNA Analysis of Polysomes from Isolated Mouse Heart After Langendorff Perfusion
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Dynamic Proteomic and miRNA Analysis of Polysomes from Isolated Mouse Heart After Langendorff Perfusion

Published on: August 29, 2018

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Integrated Analysis of lncRNA-miRNA-mRNA Regulatory Network in Rapamycin-Induced Cardioprotection against

Arun Samidurai1, Amy L Olex2, Ramzi Ockaili1

  • 1Division of Cardiology, Pauley Heart Center, Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.

Cells
|December 22, 2023
PubMed

Insights

Rapamycin (RAPA) protects diabetic hearts from ischemia/reperfusion (I/R) injury by modulating microRNA (miRNA) and long non-coding RNA (lncRNA) expression. This study identifies key miRNAs and lncRNAs regulated by RAPA, offering potential therapeutic targets for diabetic myocardial infarction.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Genomics and Transcriptomics

Background:

  • Diabetes mellitus exacerbates myocardial ischemia/reperfusion (I/R) injury.
  • Mammalian target of rapamycin (mTOR) inhibition with rapamycin (RAPA) shows protective effects in diabetic hearts.
  • Transcriptional interactions involving long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) are critical in disease pathophysiology.

Purpose of the Study:

  • To identify differentially expressed miRNAs and their predicted lncRNA/mRNA targets in diabetic rabbit hearts following I/R injury.
  • To investigate the regulatory effects of RAPA treatment on these molecular changes.
  • To explore the potential therapeutic implications of these findings for diabetic myocardial infarction.

Main Methods:

  • Unbiased miRarray profiling was performed on diabetic rabbit hearts subjected to I/R injury with or without RAPA treatment.
  • Bioinformatic analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were utilized.
  • Expression levels of specific lncRNAs (HOTAIR, GAS5, MALAT1) and their associated miRNA/mRNA targets (miR-199a-5p, Bcl-2) were analyzed.

Main Results:

  • 194 differentially expressed miRNAs were identified post-I/R in diabetic hearts; RAPA treatment reversed these changes.
  • Enrichment analyses implicated miRNAs in MAPK signaling and apoptosis pathways relevant to I/R injury.
  • RAPA modulated lncRNA expression (suppressed HOTAIR/GAS5, recovered MALAT1) and affected the miR-199a-5p/Bcl-2 axis, suggesting a mechanism for cardioprotection.

Conclusions:

  • RAPA exerts cardioprotective effects in diabetic I/R injury by modulating a network of miRNAs and lncRNAs.
  • The identified miRNA-lncRNA interactions, particularly involving MALAT1 and miR-199a-5p, represent potential therapeutic targets.
  • These findings may pave the way for novel treatment strategies for diabetic patients suffering from myocardial infarction.
Keywords:
MALAT1apoptosisdiabetesischemia/reperfusion injurylong non-coding RNAsmRNAsmTORmicroRNAsrapamycin

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