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 |
|---|---|
| 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
Cite this
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Nicotinic acetylcholine receptor alpha 7 stimulation dampens splenic myelopoiesis and inhibits atherogenesis in Apoe−/− mice. / Al-Sharea, Annas; Lee, Man K.S.; Whillas, Alexandra; Flynn, Michelle C.; Chin-Dusting, Jaye; Murphy, Andrew J.
In: Atherosclerosis, Vol. 265, 01.10.2017, p. 47-53.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Nicotinic acetylcholine receptor alpha 7 stimulation dampens splenic myelopoiesis and inhibits atherogenesis in Apoe−/− mice
AU - Al-Sharea, Annas
AU - Lee, Man K.S.
AU - Whillas, Alexandra
AU - Flynn, Michelle C.
AU - Chin-Dusting, Jaye
AU - Murphy, Andrew J.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - Alpha 7 nicotinic acetylcholine receptor
KW - Atherosclerosis
KW - Inflammation
KW - Myelopoiesis
UR - http://www.scopus.com/inward/record.url?scp=85028346144&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2017.08.010
DO - 10.1016/j.atherosclerosis.2017.08.010
M3 - Article
VL - 265
SP - 47
EP - 53
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
ER -