Projects per year
Abstract
Background and aims Monocyte levels predict cardiovascular outcomes and play a causal role in atherogenesis. Monocytes can be produced in the spleen and track to the atherosclerotic lesion in significant numbers. The cholinergic system has been shown to have anti-inflammatory actions in the spleen. We aimed to explore whether therapeutic stimulation of the nicotinic acetylcholine receptor alpha 7 (nAChRα7) can suppress atherogenesis. Methods Apoe−/− mice were placed on a Western-type diet and treated with bi-daily injections of the nAChRα7 agonist GTS-21 or vehicle every 2–3 days for 8 weeks. Results GTS-21 caused a reduction in atherosclerosis in the aortic arch and proximal aorta. This also resulted in less plaque macrophages. Moreover, GTS-21 reduced the abundance of blood monocytes, which was caused by inhibition of inflammatory cytokines and extramedullary hematopoiesis in the spleen, along with splenic monocytes. Conclusions Stimulation of nAChRα7 with GTS-21 reduced atherosclerosis, which was associated with dampened splenic myelopoiesis.
Original language | English |
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Pages (from-to) | 47-53 |
Number of pages | 7 |
Journal | Atherosclerosis |
Volume | 265 |
DOIs | |
Publication status | Published - 1 Oct 2017 |
Keywords
- Alpha 7 nicotinic acetylcholine receptor
- Atherosclerosis
- Inflammation
- Myelopoiesis
Projects
- 1 Finished
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Investigation into the intervention of arterial thrombosis and atherosclerosis using shear sensitive nanoparticle drug delivery
Westein, E. & Murphy, A. J.
1/04/17 → 30/06/18
Project: Research