Translational Stroke Research

, Volume 10, Issue 3, pp 298–307 | Cite as

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

  • Wan Jiang
  • Wei Hu
  • Li Ye
  • Yanghua Tian
  • Ren Zhao
  • Juan Du
  • Bing ShenEmail author
  • Kai Wang
Original Article


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 apelin-17 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.


Stroke Apelin-17 Cerebral collateral circulation Basilar artery Endothelium Nitric oxide Cerebral ischemic protection 



The authors would like to thank Lei Zhan for editing the English text in a draft of this manuscript.

Funding Information

The present study was supported by grants from the National Key Research and Development Program of China (2016YFC1300600); Natural Science Foundation of China (Grant No. 81371284, 81570403, 81600286); Overseas Scholars Start Fund from Department of Human Resources and Social Security of Anhui Province; Outstanding Young Investigator of Anhui Medical University; Anhui Provincial Natural Science Foundation (Grant Nos. 1708085MH187, 1508085QH164).

Compliance with Ethical Standards

Research Involving Animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • 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
    Email author
  • Kai Wang
    • 1
    • 2
    • 3
  1. 1.Department of NeurologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Anhui Province Key Laboratory of Cognition and Neuropsychiatric DisordersHefeiChina
  3. 3.Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental HealthHefeiChina
  4. 4.Department of NeurologyAffiliated Provincial Hospital of Anhui Medical UniversityHefeiChina
  5. 5.Department of CardiologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
  6. 6.School of Basic Medical SciencesAnhui Medical UniversityHefeiChina

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