| First Author | Li X | Year | 2020 |
| Journal | Int Immunopharmacol | Volume | 80 |
| Pages | 106116 | PubMed ID | 31978804 |
| Mgi Jnum | J:298490 | Mgi Id | MGI:6480176 |
| Doi | 10.1016/j.intimp.2019.106116 | Citation | Li X, et al. (2020) Inhibition of Dectin-1 in mice ameliorates cardiac remodeling by suppressing NF-kappaB/NLRP3 signaling after myocardial infarction. Int Immunopharmacol 80:106116 |
| abstractText | 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-kappaB (NF-kappaB), 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-kappaB, repressed the activation of NF-kappaB, 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-kappaB and NLRP3. This study identified Dectin-1 as a promising therapeutic target for ischemic heart disease. |
