Contribution of Apelin-17 to Collateral Circulation Following Cerebral Ischemic Stroke

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ORIGINAL ARTICLE

Contribution of Apelin-17 to Collateral Circulation Following Cerebral Ischemic Stroke Wan Jiang 1,2,3 & Wei Hu 4 & Li Ye 1,2,3 & Yanghua Tian 1,2,3 & Ren Zhao 5 & Juan Du 6 & Bing Shen 6 & Kai Wang 1,2,3 Received: 30 August 2017 / Revised: 7 June 2018 / Accepted: 12 June 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract Apelin, an essential mediator of homeostasis, is crucially involved in cardiovascular diseases, including ischemic stroke. However, the functional roles of apelin-17 in cerebral collateral circulation and ischemic stroke protection are unknown. Here, we investigated the association between plasma apelin-17 levels and collateral circulation in patients with ischemic stroke and examined the mechanism undergirding the effects of apelin-17 on cerebral artery contraction and ischemic stroke protection in an animal model. Plasma nitric oxide (NO), apelin-17, and apelin-36 levels were assessed by enzyme-linked immunosorbent assays in ischemic stroke patients with good or poor collateral circulation and in healthy participants. Additionally, the effects of apelin17 on rat basilar artery contractions (in vitro) and cerebral ischemia (in vivo) were determined using vessel tension measurements and nuclear magnetic resonance, respectively. Patients with good collateral circulation had significantly higher plasma apelin-17 and apelin-36 levels than both patients with poor collateral circulation and healthy participants and plasma NO levels significantly higher than those in healthy participants. In vitro, apelin-17 pretreatment markedly attenuated U46619-induced rat basilar artery contractions in an endothelium-dependent manner. Additionally, NO production or guanylyl cyclase inhibitors abolished the apelin-17 effect on U46619-induced vascular contraction. Intravenous pretreatment of rats with apelin-17 markedly reduced cerebral infarct volume at 24 h after middle cerebral artery occlusion. Plasma apelin-17 levels in ischemic stroke patients were positively associated with enhanced collateral circulation, which our animal study data suggested may have resulted from an apelin-17-induced cerebral artery dilation mediated through the NO–cGMP pathway. Keywords Stroke . Apelin-17 . Cerebral collateral circulation . Basilar artery . Endothelium . Nitric oxide . Cerebral ischemic protection

Introduction Ischemic stroke is a leading cause of death in humans worldwide [1]. When the proximal artery becomes occluded, fresh blood is delivered to the ischemic area

through collateral circulation, reducing cerebral damage [2, 3]. A rich supply of blood through collateral circulation can reduce expansion of the ischemic area and improve clinical outcomes [4]. Accumulating clinical evidence suggests that the functional status of the collateral

Wan Jiang and Wei Hu contributed equally to this work and shared first authorship * Bing Shen [email protected] Kai Wang [email protected] 1

2

Department of Neurology, The First Affiliated Hospital of Anhui Medical University,