title: Semaphorin 3a transfection into the left stellate ganglion reduces susceptibility to ventricular arrhythmias after myocardial infarction in rats.
abstract: OBJECTIVE
  Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling.
  
  
  RESULTS
  Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups.
  
  
  CONCLUSIONS
  Semaphorin 3a overexpression in the LSG ameliorates the inducibility of ventricular arrhythmias after MI, mainly through attenuation of neural remodelling within the cardiac-neuraxis.
authors.affiliation: Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Ling-Chao
authors.initials: LC
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Peng-Pai
authors.initials: PP
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Hou
authors.affiliation: Department of Cardiology, Ganzhou People Hospital, Ganzhou Hospital Affiliated to Nanchang University, Ganzhou, Jiangxi 341000, China.
authors.forename: Ren-Hua
authors.initials: RH
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Yue-Peng
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China drliyigang@outlook.com.
authors.forename: Yi-Gang
authors.initials: YG
authors.lastname: Li
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D004562:Electrocardiography; D015316:Genetic Therapy; D006321:Heart / Q000294:innervation; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D040121:Semaphorin-3A / Q000235:genetics / Q000627:therapeutic use*; D013233:Stellate Ganglion / Q000187:drug effects / Q000378:metabolism*; D017180:Tachycardia, Ventricular / Q000628:therapy*; D014162:Transfection
chemical_list: D040121:Semaphorin-3A; D009638:Norepinephrine
keywords: Myocardial infarction; Semaphorin 3a; Stellate ganglion; Ventricular arrhythmias