title: Vagus nerve stimulation attenuates myocardial ischemia/reperfusion injury by inhibiting the expression of interleukin-17A.
abstract: Interleukin (IL)-17A has an important role in myocardial ischemia/reperfusion (I/R) injury, and vagal stimulation (VS) has been demonstrated to exert cardioprotective effects. The present study aimed to investigate the effects of VS on a rat model of myocardial I/R injury, and detected an association between VS and IL-17A. Anesthetized rats underwent VS (2 msec; 10 Hz) or were treated with anti-IL-17A neutralized monoclonal antibodies (mAbs) (200 µg; iv), and subjected to ischemia for 30 min prior to 4 h reperfusion. The following parameters were measured: Infarct size; lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activity levels; tumor necrosis factor (TNF)-α and IL-6 expression levels; and the percentage of terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) positive cells. High mobility group box 1 protein (HMGB1) and IL-17A expression levels were assessed by immunoblotting. Following 4 h reperfusion, VS was able to significantly decrease the infarct size and the activity levels of LDH and CK (P<0.05). Furthermore, VS administration significantly suppressed the increased MDA and decreased SOD activity levels, and significantly reduced caspase-3 activity and the percentage of TUNEL-positive cells (P<0.05). Treatment with anti-IL-17A mAbs demonstrated the same effects as VS. Furthermore, VS was able to significantly inhibit the increased expression levels of TNF-α, IL-6, HMGB1 and IL-17A induced by I/R (P<0.05). The results of the present study suggested that VS may attenuate myocardial I/R injury by reducing the expression of inflammatory cytokines, oxidative stress and the apoptosis of cardiomyocytes. Furthermore, VS may induce cardioprotective effects, which may be associated with the inhibition of IL-17A expression.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Yi
authors.affiliation: Department of Cardiology, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Weipan
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yuanxi
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Ruisong
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Wang
keywords: inflammation; interleukin-17A; myocardial ischemia; reperfusion; vagal stimulation