title: Baroreflex deficiency aggravates atherosclerosis via α7 nicotinic acetylcholine receptor in mice.
abstract: 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.
  
  
  
  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.
  
  
  
  Our results demonstrate that ABR dysfunction aggravates atherosclerosis in mice via the vagus-ACh-α7nAChR-inflammation and oxidative stress pathway.
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.
authors: Li
authors: L
authors: Chen
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.
authors: Dian-Hua
authors: DH
authors: Liu
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.
authors: Xin
authors: X
authors: Zhang
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.
authors: En-Hui
authors: EH
authors: Zhang
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.
authors: Chong
authors: C
authors: Liu
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China.
authors: Ding-Feng
authors: DF
authors: Su
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai, China. Electronic address: cai_gj@yahoo.com.
authors: Guo-Jun
authors: GJ
authors: Cai
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001158:Arteries / Q000502:physiology; D050197:Atherosclerosis / Q000473:pathology*; D017704:Baroreflex / Q000502:physiology*; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology*; D007650:Ketanserin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; C498513:PNU-282987; D064569:alpha7 Nicotinic Acetylcholine Receptor; D007650:Ketanserin
keywords: Arterial baroreflex; Atherosclerosis; Inflammation; Oxidative stress; α7nAChR