Nicotinic acetylcholine receptor alpha 7 stimulation dampens splenic myelopoiesis and inhibits atherogenesis in Apoe−/− mice

Annas Al-Sharea, Man K.S. Lee, Alexandra Whillas, Michelle C. Flynn, Jaye Chin-Dusting, Andrew J. Murphy

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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 languageEnglish
Pages (from-to)47-53
Number of pages7
JournalAtherosclerosis
Volume265
DOIs
Publication statusPublished - 1 Oct 2017

Keywords

  • Alpha 7 nicotinic acetylcholine receptor
  • Atherosclerosis
  • Inflammation
  • Myelopoiesis

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