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Baroreflex deficiency aggravates atherosclerosis via α7 nicotinic acetylcholine receptor in mice.
Vascul Pharmacol. 2016 12; 87:92-99.VP

Abstract

OBJECTIVE

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 RESULTS

ApoE-/- mice were fed with a high-cholesterol diet for 6weeks 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, 0.53mg/kg/day) for 6weeks 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 8weeks were co-treated with ketanserin (0.6mg/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.

CONCLUSIONS

Our results demonstrate that ABR dysfunction aggravates atherosclerosis in mice via the vagus-ACh-α7nAChR-inflammation and oxidative stress pathway.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China. Electronic address: cai_gj@yahoo.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27568460

Citation

Chen, Li, et al. "Baroreflex Deficiency Aggravates Atherosclerosis Via Α7 Nicotinic Acetylcholine Receptor in Mice." Vascular Pharmacology, vol. 87, 2016, pp. 92-99.
Chen L, Liu DH, Zhang X, et al. Baroreflex deficiency aggravates atherosclerosis via α7 nicotinic acetylcholine receptor in mice. Vascul Pharmacol. 2016;87:92-99.
Chen, L., Liu, D. H., Zhang, X., Zhang, E. H., Liu, C., Su, D. F., & Cai, G. J. (2016). Baroreflex deficiency aggravates atherosclerosis via α7 nicotinic acetylcholine receptor in mice. Vascular Pharmacology, 87, 92-99. https://doi.org/10.1016/j.vph.2016.08.008
Chen L, et al. Baroreflex Deficiency Aggravates Atherosclerosis Via Α7 Nicotinic Acetylcholine Receptor in Mice. Vascul Pharmacol. 2016;87:92-99. PubMed PMID: 27568460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baroreflex deficiency aggravates atherosclerosis via α7 nicotinic acetylcholine receptor in mice. AU - Chen,Li, AU - Liu,Dian-Hua, AU - Zhang,Xin, AU - Zhang,En-Hui, AU - Liu,Chong, AU - Su,Ding-Feng, AU - Cai,Guo-Jun, Y1 - 2016/08/25/ PY - 2015/12/20/received PY - 2016/07/12/revised PY - 2016/08/23/accepted PY - 2016/8/29/pubmed PY - 2017/7/8/medline PY - 2016/8/29/entrez KW - Arterial baroreflex KW - Atherosclerosis KW - Inflammation KW - Oxidative stress KW - α7nAChR SP - 92 EP - 99 JF - Vascular pharmacology JO - Vascul. Pharmacol. VL - 87 N2 - OBJECTIVE: 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 RESULTS: ApoE-/- mice were fed with a high-cholesterol diet for 6weeks 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, 0.53mg/kg/day) for 6weeks 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 8weeks were co-treated with ketanserin (0.6mg/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. CONCLUSIONS: Our results demonstrate that ABR dysfunction aggravates atherosclerosis in mice via the vagus-ACh-α7nAChR-inflammation and oxidative stress pathway. SN - 1879-3649 UR - https://www.unboundmedicine.com/medline/citation/27568460/Baroreflex_deficiency_aggravates_atherosclerosis_via_α7_nicotinic_acetylcholine_receptor_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1537-1891(15)30116-6 DB - PRIME DP - Unbound Medicine ER -