Baker Heart and Diabetes Institute, Melbourne, Australia; Monash University, Melbourne, Australia.
Baker Heart and Diabetes Institute, Melbourne, Australia.
Atherosclerosis. 2017 Oct;265:47-53. doi: 10.1016/j.atherosclerosis.2017.08.010. Epub 2017 Aug 18.
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.
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.
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.
Stimulation of nAChRα7 with GTS-21 reduced atherosclerosis, which was associated with dampened splenic myelopoiesis.
单核细胞水平可预测心血管结局，并在动脉粥样硬化形成中起因果作用。单核细胞可在脾脏中产生，并以大量数量追踪到动脉粥样硬化病变。胆碱能系统已被证明在脾脏中具有抗炎作用。我们旨在探讨治疗性刺激烟碱型乙酰胆碱受体α7（nAChRα7）是否可以抑制动脉粥样硬化形成。
载脂蛋白 E 基因敲除（Apoe）小鼠给予西方饮食，并每隔 2-3 天接受烟碱型乙酰胆碱受体α7 激动剂 GTS-21 或载体的每日两次注射，共 8 周。
GTS-21 导致主动脉弓和近端主动脉的动脉粥样硬化减少。这也导致斑块中的巨噬细胞减少。此外，GTS-21 减少了血液单核细胞的丰度，这是由于抑制了脾脏中的炎症细胞因子和骨髓外造血，以及脾脏中的单核细胞。
用 GTS-21 刺激 nAChRα7 可减少动脉粥样硬化，这与脾脏中的骨髓生成减少有关。
