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Inhibition of Dectin-1 in mice ameliorates cardiac remodeling by suppressing NF-κB/NLRP3 signaling after myocardial infarction.
- Source :
-
International Immunopharmacology . Mar2020, Vol. 80, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
Abstract
- • Cardiomyocyte contributes to elevation of Dectin-1 expression post-MI. • Silencing Dectin-1 improves cardiac remodeling and function in the ischemic heart. • Dectin-1 aggravates MI induced cardiac dysfunction by partially activating NF- κ B/NLRP3 axis. The myocardial inflammatory response is a consequence of myocardial infarction (MI), which may deteriorate cardiac remodeling and lead to dysfunction in the heart post-MI. Dectin-1 is a c-type lectin, which has been shown to regulate innate immune responses to pathogens. However, the role of Dectin-1 in the heart diseases remains largely unknown. In this study, we aimed to investigate the effects of Dectin-1 on cardiac remodeling post-MI. We found that cardiac Dectin-1 mRNA and protein expressions were significantly elevated in C57BL/6 mice after MI. In vitro , hypoxia induced cardiomyocyte injury in parallel with increased Dectin-1 protein expression. Knockdown of Dectin-1 remarkably attenuated cardiomyocyte death under hypoxia and lipopolysaccharide (LPS) stimulation. In vivo administration of adeno-associated virus serotype 9 mediated silencing of Dectin-1, which significantly decreased cardiac fibrosis, dilatation, and improved cardiac function in the mice post-MI. At the molecular level, downregulation of Dectin-1 dramatically suppressed up-regulation of nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), and the inflammatory genes involved in fibrogenesis and cardiac remodeling after MI. Furthermore, treatment with BAY11-7082, an inhibitor of NF-κB, repressed the activation of NF-κB, and attenuated LPS induced elevation of NLRP3 and cell death in cardiomyocytes. Collectively, upregulation of Dectin-1 in cardiomyocytes post-MI contributes to cardiac remodeling and cardiac dysfunction at least partially by activating NF-κB and NLRP3. This study identified Dectin-1 as a promising therapeutic target for ischemic heart disease. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 80
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 141755038
- Full Text :
- https://doi.org/10.1016/j.intimp.2019.106116