Necrotic Cell Sensor Clec4e Promotes a Proatherogenic Macrophage Phenotype Through Activation of the Unfolded Protein Response
Authors' conclusion
Our results identify a nonredundant role for Clec4e in coordinating major biological pathways involved in atherosclerosis
Study context
- Population
- Macrophages in vitro and Ldlr-/- mice; human and mouse atherosclerotic lesions
- Comparison
- Clec4e activation/deficiency vs control in macrophages and Ldlr-/- mice
Methodological detailsin vitro, in vivo mouse model
- In vitro
- In vivo mouse model
Main finding
As reported in the abstract
- Clec4e expressed within human and mouse atherosclerotic lesions and activated by necrotic lesion extracts
- Clec4e signalling in macrophages inhibits cholesterol efflux and induces Syk-mediated ER stress response, inducing proinflammatory mediators and growth factors
- Chop and Ire1a deficiencies significantly limit Clec4e-dependent effects; Atf3 deficiency aggravates Clec4e-mediated inflammation and altered cholesterol efflux
- Clec4e-/- bone marrow in Ldlr-/- mice reduces lesional lipid accumulation, ER stress, macrophage inflammation and proliferation, and significantly limits atherosclerosis
Original publication
Necrotic Cell Sensor Clec4e Promotes a Proatherogenic Macrophage Phenotype Through Activation of the Unfolded Protein Response. Circulation. Published 1 September 2016. doi:10.
Summarised from the published abstract; every number is checked against it