Baroreflex deficiency aggravates atherosclerosis via α7 nicotinic acetylcholine receptor in mice

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• 作者：Li Chen¹ ; Dian-Hua Liu¹ ; Xin Zhang ; En-Hui Zhang ; Chong Liu ; Ding-Feng Su ; Guo-Jun Cai ; ^{cai_gj@yahoo.com}
• 关键词：α7nAChR ; Atherosclerosis ; Oxidative stress ; Inflammation ; Arterial baroreflex
• 刊名：Vascular Pharmacology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：87
• 期：Complete
• 页码：92-99
• 全文大小：958 K
• 卷排序：87

文摘

Inflammation and oxidative stress play a key role in the initiation, propagation, and development of atherosclerosis. Arterial baroreflex (ABR) dysfunction induced by sinoaortic denervation (SAD) promoted the development of atherosclerosis in ApoE−/− mice. The present work was designed to examine whether ABR deficiency affected inflammation and oxidative stress via α7 nicotinic acetylcholine receptor (α7nAChR) leading to the aggravation of atherosclerosis in mice.Methods and resultsApoE−/− mice were fed with a high-cholesterol diet for 6 weeks and half of the mice received sinoaortic denervation that destroyed ABR. We studied the expression of vesicular acetylcholine transporter (VAChT), α7nAChR and levels of inflammatory response and oxidative stress. The results showed that baroreflex dysfunction could promote atherosclerosis, meanwhile, decrease the expression of VAChT and α7nAChR and significantly increase the levels of oxidative stress and inflammation in SAD mice. After treated with PNU-282987 (a selective α7nAChR agonist, 0.53 mg/kg/day) for 6 weeks in SAD and Sham mice, we found that PNU-282987 could attenuate atherosclerosis and significantly decreased oxidative stress and inflammation after SAD. In addition, α7nAChR+/+ and α7nAChR−/− mice fed with a high-cholesterol diet for 8 weeks were co-treated with ketanserin (0.6 mg/kg/day), a drug that can enhance baroreflex sensitivity (BRS). Ketanserin could alleviate atherosclerosis and markedly decrease oxidative stress and inflammation in α7nAChR+/+ mice. But there were no effects in α7nAChR knockout mice.ConclusionsOur results demonstrate that ABR dysfunction aggravates atherosclerosis in mice via the vagus-ACh-α7nAChR-inflammation and oxidative stress pathway.