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Published on: December 10, 2016
Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1
Praveena S Thiagarajan1, Valentin P Yakubenko, Deena H Elsori
1Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA.
Cardiovascular Research
|May 16, 2013
Summary
Vimentin acts as an endogenous ligand for Dectin-1, promoting superoxide production in atherosclerosis. This finding reveals a new pathway contributing to cholesterol buildup and inflammation in artery walls.
Area of Science:
- Immunology
- Cardiovascular Research
- Cell Biology
Background:
- Atherosclerosis involves cholesterol deposition in macrophages, leading to arterial wall inflammation and lumen narrowing.
- Monocyte-derived macrophages (MDM) in lesions produce superoxide anion (O₂⁻), oxidizing low-density lipoprotein (LDL) and causing foam cell formation.
- Dectin-1, a pattern recognition receptor (PRR), activates monocyte NADPH oxidase, but its endogenous ligands in atherosclerosis are unknown.
Purpose of the Study:
- To identify endogenous ligands for Dectin-1 involved in inflammation-driven superoxide production in atherosclerosis.
- To investigate the role of these ligands in activating Dectin-1 and contributing to atherogenesis.
Main Methods:
- Used anti-zymosan antibodies to probe human atherosclerotic tissue extracts for cross-reactive epitopes.
- Performed immunoblot and mass spectrometry to identify proteins binding to the antibodies.
- Utilized BIACORE for direct binding analysis of identified proteins to Dectin-1.
- Assessed the ability of identified proteins to induce O₂⁻ production in human monocytes.
- Examined the localization of identified proteins and Dectin-1 in human atherosclerotic lesions.
Main Results:
- Vimentin was identified as a protein that cross-reacts with anti-zymosan antibodies in atherosclerotic tissues.
- Vimentin directly binds to Dectin-1 and induces superoxide anion (O₂⁻) production in human monocytes.
- Extracellular vimentin was detected in necrotic cores and inflammatory areas of atherosclerotic lesions.
- Vimentin co-localized with Dectin-1 in macrophage-rich regions associated with O₂⁻ production.
Conclusions:
- Vimentin is identified as an endogenous activating ligand for the Dectin-1 receptor.
- Vimentin's presence in atherosclerotic lesions suggests it contributes to Dectin-1-mediated O₂⁻ production.
- This mechanism highlights vimentin's role in lipid oxidation and cholesterol accumulation, key processes in atherosclerosis development.
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