Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms
Authors' conclusion
Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis
Study context
- Population
- Mice with AAV-mutant PCSK9-induced atherosclerosis; human atherosclerotic lesions and PBMCs from atherosclerotic patients
- Comparison
- Macrophage-specific NFATc3 knockout or transgenic mice vs controls
Methodological detailsmacrophage-specific NFATc3 knockout and transgenic mice, AAV-mutant PCSK9-induced atherosclerosis model
- Macrophage-specific NFATc3 knockout and transgenic mice
- AAV-mutant PCSK9-induced atherosclerosis model
Main finding
As reported in the abstract
- NFATc3 expression decreased in macrophages within human and mouse atherosclerotic lesions
- NFATc3 levels in PBMCs from atherosclerotic patients negatively associated with plaque instability
- Macrophage-specific NFATc3 ablation led to atherosclerotic plaque formation; macrophage-specific NFATc3 transgenic mice showed the opposite phenotype
- NFATc3 deficiency promoted foam cell formation by potentiating SR-A- and CD36-mediated lipid uptake
- NFATc3 directly targeted and transcriptionally up-regulated miR-204; miR-204-5p suppressed SR-A; nuclear miR-204-3p inhibited CD36 transcription
- Restoring miR-204 abolished the proatherogenic phenotype of NFATc3 knockout mice; blocking miR-204 reversed the beneficial effects of NFATc3
Original publication
Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms. Eur Heart J. Published 27 September 2021. doi:10.
Summarised from the published abstract; every number is checked against it