Nrf2 attenuates the innate immune response after experimental myocardial infarction.
Biochem Biophys Res Commun
; 606: 10-16, 2022 05 28.
Article
de En
| MEDLINE
| ID: mdl-35338853
ABSTRACT
BACKGROUND:
There is compelling evidence implicating dysregulated inflammation in the mechanism of ventricular remodeling and heart failure (HF) after MI. The transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2, encoded by Nfe2l2) is a promising target in this context since it impedes transcriptional upregulation of pro-inflammatory cytokines and is anti-inflammatory in various murine models.OBJECTIVES:
We aimed to investigate the contribution of Nrf2 to the inflammatory response after experimental myocardial infarction (MI).METHODS:
We subjected Nrf2-/- mice and wild type (WT) controls to permanent left coronary artery (LCA) ligation. The inflammatory response was investigated with fluorescence-activated cell sorting (FACS) analysis of peripheral blood and heart cell suspensions, together with qRT-PCR of infarcted tissue for chemokines and their receptors. To investigate whether Nrf2-mediated transcription is a dedicated function of leukocytes, we interrogated publicly available RNA-sequencing (RNA-seq) data from mouse hearts after permanent LCA ligation for Nrf2-regulated gene (NRG) expression.RESULTS:
FACS analysis demonstrated a profoundly inflamed phenotype in the hearts of global Nrf2-/- mice as compared to WT mice after MI. Moreover, infarcted tissue from Nrf2-/- mice displayed higher expression of mRNA coding for inflammatory cytokines, chemokines, and their receptors, including IL-6, Ccl2, and Cxcr4. RNA-seq analysis showed upregulated NRG expression in WT mice after MI compared to naive mice, which was significantly higher in bioinformatically isolated CCR2+ cells.CONCLUSIONS:
Taken together, the results suggest that Nrf2 signalling in leukocytes, and possibly CCR2+ monocytes and monocyte-derived cardiac resident macrophages, may be potential targets to prevent post-MI ventricular remodeling.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Remodelage ventriculaire
/
Facteur-2 apparenté à NF-E2
/
Infarctus du myocarde
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Biochem Biophys Res Commun
Année:
2022
Type de document:
Article