The Mechanism of miR-142-3p in Coronary Microembolization-Induced Myocardiac Injury via Regulating Target Gene IRAK-1

Cell Death Dis. 2019 Jan 25;10(2):61. doi: 10.1038/s41419-019-1341-7.

Abstract

Coronary microembolization (CME) is a common complication seen during primary percutaneous coronary intervention (pPCI). CME-induced myocardiac inflammation is the primary cause of myocardiac injury. Dysregulated miR-142-3p has been implicated in multiple cardiovascular diseases and is significantly downregulated in CME-induced myocardial injury. However, the role of miR-142-3p in CME-induced myocardial injury is unclear. This study herein built a porcine CME model by infusing microembolization spheres into the left anterior descending branch via a microcatheter, and detected the downregulation of miR-142-3p in the myocardial tissues of CME pigs. Echocardiography, hematoxylin basic fuchsin picric acid (HBFP) staining, and western blotting of NF-κB p65, TNF-α, IL-1β, and IL-6 showed that the pharmacological overexpression of miR-142-3p using agomiR has improved cardiac function and attenuated CME-induced myocardiac inflammatory response, while its inhibition using antagomiR demonstrated inverse effects. Moreover, in vitro experiments demonstrated IRAK-1 as a direct target gene of miR-142-3p. Luciferase reporter assays, quantitative real-time polymerase chain reaction and western blotting demonstrated its effects in controlling the inflammation of cardiomyocytes. It is noteworthy that miR-142-3p was found to be decreased in the plasma of STEMI patients undergoing pPCI with no-reflow, indicating a potential clinical relevance of miR-142-3p. The receiver-operator characteristic curve indicated that plasma miR-142-3p might be an independent predictor of no-reflow during pPCI in patients with STEMI. Therefore, overexpression of miR-142-3p acts as a novel therapy for CME-induced myocardial injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Embolism / complications*
  • Embolism / etiology
  • Female
  • HEK293 Cells
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / genetics*
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Lipopolysaccharides / pharmacology
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocardial Infarction / surgery
  • Myocarditis / blood*
  • Myocarditis / etiology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Percutaneous Coronary Intervention / adverse effects
  • Rats
  • Swine
  • Transcription Factor RelA / metabolism
  • Transfection

Substances

  • Cytokines
  • Lipopolysaccharides
  • MIRN142 microRNA, human
  • MIRN142 microRNA, rat
  • MicroRNAs
  • RELA protein, human
  • Rela protein, rat
  • Transcription Factor RelA
  • IRAK1 protein, human
  • IRAK1 protein, rat
  • Interleukin-1 Receptor-Associated Kinases