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

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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 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.

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Acknowledgements

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

Funding

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).

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Author notes

  1. Wan Jiang and Wei Hu contributed equally to this work and shared first authorship

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China

    Wan Jiang, Li Ye, Yanghua Tian & Kai Wang

  2. Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230032, Anhui, China

    Wan Jiang, Li Ye, Yanghua Tian & Kai Wang

  3. Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, 230032, Anhui, China

    Wan Jiang, Li Ye, Yanghua Tian & Kai Wang

  4. Department of Neurology, Affiliated Provincial Hospital of Anhui Medical University, Hefei, 230032, Anhui, China

    Wei Hu

  5. Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China

    Ren Zhao

  6. School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui, China

    Juan Du & Bing Shen

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  1. Wan Jiang
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Correspondence to Bing Shen.

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

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Jiang, W., Hu, W., Ye, L. et al. Contribution of Apelin-17 to Collateral Circulation Following Cerebral Ischemic Stroke. Transl. Stroke Res. 10, 298–307 (2019). https://doi.org/10.1007/s12975-018-0638-7

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