Constitutive activation of the NEAT1/miR-22-3p/Ltb4r1 signaling pathway in mice with myocardial injury following acute myocardial infarction

Aging (Albany NY). 2021 Jun 3;13(11):15307-15319. doi: 10.18632/aging.203089. Epub 2021 Jun 3.

Abstract

Coronary heart disease (CHD) with myocardial infarction (MI) being the manifestation of its advanced manifestation, remains the primary cause of mortality and disability worldwide. Aberrant expression of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) can affect the occurrence of MI in CHD. The present study aimed to explore whether NEAT1 sponging with miR-22-3p affected MI in CHD and its related mechanism. We established that the NEAT1 and Ltb4r1 expressions were increased, while miR-22-3p expression was down-regulated in MI mice following CHD. NEAT1 could competitively bind to miR-22-3p and positively regulate Ltb4r1 expression. Ltb4r1 was the downstream target of miR-22-3p. Moreover, silencing NEAT1 or downregulating Ltb4rl expression resulted in improved cardiac function, reduced infarct size, and declined levels of IL-1β, IL-6, and IL-18. Furthermore, silencing of NEAT1 also inhibited apoptosis by decreasing levels of Cleaved caspase-3 and Bax, and increasing Bcl-2 level through sponging miR-22-3p, resulting in reduced myocardial injury in CHD. Altogether, the activation of the NEAT1/miR-22-3p/Ltb4r1 signaling pathway appears to aggravate myocardial injury following a MI, which suggested that this signaling may be a useful target for improved and more individualized treatments for MI.

Keywords: Ltb4rl; NEAT1; long non-coding RNAs; microRNA-22-3p; myocardial infarction.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Down-Regulation / genetics
  • Gene Silencing
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / pathology*
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, Leukotriene B4 / metabolism*
  • Signal Transduction*
  • Up-Regulation / genetics

Substances

  • Ltb4r1 protein, mouse
  • MicroRNAs
  • Mirn22 microRNA, mouse
  • NEAT1 long non-coding RNA, mouse
  • RNA, Long Noncoding
  • Receptors, Leukotriene B4