Macrophage P2Y6 receptor deletion attenuates atherosclerosis by limiting foam cell formation through phospholipase Cβ/store-operated calcium entry/calreticulin/scavenger receptor A pathways
Authors' conclusion
Macrophage P2Y6R regulates phospholipase Cβ/store-operated calcium entry/calreticulin signalling pathway to increase scavenger receptor A protein level, thereby improving foam cell formation and atherosclerosis
Study context
- Population
- Atherosclerosis mouse models; human atherosclerotic plaques
- Comparison
- P2Y6 receptor (P2Y6R) deletion vs intact P2Y6R
Methodological detailswhole-body and macrophage-specific P2Y6R knockout mice, human atherosclerotic plaques, RNA sequencing, DNA pull-down, proteomics, high-throughput Glide docking of repurposing drug library
- Whole-body and macrophage-specific P2Y6R knockout mice
- Human atherosclerotic plaques
- RNA sequencing, DNA pull-down, proteomics
- High-throughput Glide docking of repurposing drug library
Main finding
As reported in the abstract
- P2Y6R deficiency alleviated atherogenesis: decreased aortic plaque formation and lipid deposition
- Macrophage P2Y6R deletion inhibited oxidized LDL uptake via decreased scavenger receptor A expression mediated by phospholipase Cβ/store-operated calcium entry
- P2Y6R deficiency reduced scavenger receptor A binding to CALR, with dissociation of calreticulin and STIM1
- Thiamine pyrophosphate identified as potent P2Y6R antagonist; pharmacodynamic effect and mechanism on atherosclerosis verified
Original publication
Macrophage P2Y6 receptor deletion attenuates atherosclerosis by limiting foam cell formation through phospholipase Cβ/store-operated calcium entry/calreticulin/scavenger receptor A pathways. Eur Heart J. Published 30 November 2023. doi:10.
Summarised from the published abstract; every number is checked against it