Resveratrol attenuates pulmonary embolism associated cardiac injury by suppressing activation of the inflammasome via the MALAT1‑miR‑22‑3p signaling pathway

Int J Mol Med. 2019 Dec;44(6):2311-2320. doi: 10.3892/ijmm.2019.4358. Epub 2019 Oct 1.

Abstract

Resveratrol (RS) has been reported to prevent the development of cardiac injury induced by pulmonary embolism (PE). The present study aimed to explore the potential mechanism of RS involved in cardiac injury induced by PE. A luciferase assay was conducted to detect the effect of RS on promoter efficiency of metastasis associated lung adenocarcinoma transcript 1 (MALAT1), in‑silico analysis and luciferase assays were performed to explore the regulatory relationship between MALAT1, microRNA (miR)‑22‑3p and NLRP3. Reverse transcription PCR, western blot analysis and ELISA were carried out to examine MALAT1, miR‑22‑3p, NLRP3, ASC, Caspase‑1, interleukin (IL)‑1β and IL‑18 among different animal model groups, including the sham group, PE associated cardiac injury group and PE associated cardiac injury plus RS group. The results revealed that RS downregulated promoter efficiency of MALAT1 and MALAT1 directly targeted miR‑22‑3p, and luciferase activity of MALAT1 was inhibited by miR‑22‑3p, and furthermore miR‑22‑3p inhibited the expression of NLRP3 by binding to complementary sequences in the 3' untranslated region of NLRP3. MALAT1, NLRP3, ASC, Caspase‑1, IL‑1β and IL‑18 levels were much increased, while miR‑22‑3p level was much decreased in PE associated cardiac injury group compared with the sham group, while the RS upon the PE associated cardiac injury group slightly reduced the upregulated MALAT1/NLRP3 level and elevated the downregulated miR‑22‑3p level. In conclusion, it was demonstrated that RS has been demonstrated to prevent the development of cardiac injury induced by PE via modulating the expression of MALAT1 and further affect miR‑22‑3p and NLRP3.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspase 1 / genetics
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects
  • Heart Injuries / complications
  • Heart Injuries / drug therapy*
  • Heart Injuries / genetics
  • Heart Injuries / pathology
  • Humans
  • Inflammasomes / drug effects
  • Inflammasomes / genetics
  • Interleukin-18 / genetics
  • Interleukin-1beta / genetics
  • MicroRNAs / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • Pulmonary Embolism / complications
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / genetics
  • Pulmonary Embolism / pathology
  • RNA, Long Noncoding / genetics*
  • Rats
  • Resveratrol / pharmacology
  • Signal Transduction / drug effects

Substances

  • IL1B protein, rat
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • MALAT1 long noncoding RNA, rat
  • MIRN22 microRNA, rat
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • RNA, Long Noncoding
  • Caspase 1
  • Resveratrol