Dectin-1 Acts as a Non-Classical Receptor of Ang II to Induce Cardiac Remodeling

Circ Res. 2023 Mar 17;132(6):707-722. doi: 10.1161/CIRCRESAHA.122.322259. Epub 2023 Feb 14.


Background: Cardiac remodeling in heart failure involves macrophage-mediated immune responses. Recent studies have shown that a PRR (pattern recognition receptor) called dectin-1, expressed on macrophages, mediates proinflammatory responses. Whether dectin-1 plays a role in pathological cardiac remodeling is unknown. Here, we identified a potential role of dectin-1 in this disease.

Methods: To model aberrant cardiac remodeling, we utilized mouse models of chronic Ang II (angiotensin II) infusion. In this model, we assessed the potential role of dectin-1 through using D1KO (dectin-1 knockout) mice and bone marrow transplantation chimeric mice. We then used cellular and molecular assays to discover the underlying mechanisms of dectin-1 function.

Results: We found that macrophage dectin-1 is elevated in mouse heart tissues following chronic Ang II administration. D1KO mice were significantly protected against Ang II-induced cardiac dysfunction, hypertrophy, fibrosis, inflammatory responses, and macrophage infiltration. Further bone marrow transplantation studies showed that dectin-1 deficiency in bone marrow-derived cells prevented Ang II-induced cardiac inflammation and dysfunction. Through detailed molecular studies, we show that Ang II binds directly to dectin-1, causing dectin-1 homodimerization and activating the downstream Syk (spleen tyrosine kinase)/NF-κB (nuclear factor kappa B) signaling pathway to induce expression of inflammatory and chemoattractant factors. Mutagenesis studies identified R184 in the C-type lectin domain to interact with Ang II. Blocking dectin-1 in macrophages suppresses Ang II-induced inflammatory mediators and subsequent intercellular cross talk with cardiomyocytes and fibroblasts.

Conclusions: Our study has discovered dectin-1 as a new nonclassical receptor of Ang II and a key player in cardiac remolding and dysfunction. These studies suggest that dectin-1 may be a new target for treating hypertension-related heart failure.

Keywords: angiotensin II; dectin-1; heart failure; inflammation; macrophages; mutagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / toxicity
  • Animals
  • Fibrosis
  • Heart Failure* / metabolism
  • Hypertension*
  • Lectins, C-Type / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Cardiac / metabolism
  • NF-kappa B / metabolism
  • Ventricular Remodeling / physiology


  • dectin 1
  • Lectins, C-Type
  • NF-kappa B
  • Angiotensin II