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The Association Between Serum Apelin-13 and the Prognosis of Acute Ischemic Stroke

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Abstract

While a number of studies have reported an association between apelin-13 and ischemic stroke, few have verified its clinical effect. We investigated the prognostic value of serum apelin-13 levels in patients with acute ischemic stroke (AIS). We prospectively recruited 244 AIS patients within 24 h after stroke onset, and 167 healthy controls. We assessed the serum apelin-13 levels using ELISA, and the severity of AIS using the National Institutes of Health Stroke Scale (NIHSS). The primary outcomes included death or major disability (modified Rankin Scale score, 3–6) and major disability (modified Rankin Scale score, 3–5). Secondary outcomes included recurrent stroke and combined events (all-cause death, or cardiovascular and cerebrovascular events). We found that the serum apelin-13 levels in the patients (38.63 ng/mL (interquartile range [IQR], 29.86–50.99)) were lower than those in the healthy controls (42.50 ng/mL [IQR, 31.25–59.17]) (P = 0.017). Patients with a NIHSS score ≤ 3 had higher apelin-13 levels than those with a NIHSS score > 3 (P = 0.048). At the 3-month follow-up, multivariate logistic regression analysis indicated an association between apelin-13 and death or major disability (OR 0.31; 95% CI 0.11–0.86; P = 0.024) and major disability (OR 0.32; 95% CI 0.11–0.90; P = 0.030). At the 1-year follow-up, the patients with high apelin-13 levels showed a lower incidence of stroke and combined events (Log-rank test P < 0.05). Our findings indicate that serum apelin-13 may be a potential prognostic biomarker for AIS.

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References

  1. Zhou M, Wang H, Zhu J, Chen W, Wang L, Liu S, et al. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet. 2016;387(10015):251–72. https://doi.org/10.1016/S0140-6736(15)00551-6.

    Article  PubMed  Google Scholar 

  2. Collaborators GBDCoD. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1151–210. https://doi.org/10.1016/S0140-6736(17)32152-9.

    Article  Google Scholar 

  3. Writing Group M, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Heart disease and stroke Statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–360. https://doi.org/10.1161/CIR.0000000000000350.

    Article  Google Scholar 

  4. Vadakkan C, Siddiqui W. Claustrophobia. StatPearls. Treasure Island: StatPearls Publishing StatPearls Publishing LLC; 2019.

    Google Scholar 

  5. Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 1998;251(2):471–6. https://doi.org/10.1006/bbrc.1998.9489.

    Article  CAS  PubMed  Google Scholar 

  6. Lee DK, Cheng R, Nguyen T, Fan T, Kariyawasam AP, Liu Y, et al. Characterization of apelin, the ligand for the APJ receptor. J Neurochem. 2000;74(1):34–41. https://doi.org/10.1046/j.1471-4159.2000.0740034.x.

    Article  CAS  PubMed  Google Scholar 

  7. Kawamata Y, Habata Y, Fukusumi S, Hosoya M, Fujii R, Hinuma S, et al. Molecular properties of apelin: tissue distribution and receptor binding. Biochim Biophys Acta. 2001;1538(2–3):162–71. https://doi.org/10.1016/s0167-4889(00)00143-9.

    Article  CAS  PubMed  Google Scholar 

  8. Zhong JC, Zhang ZZ, Wang W, McKinnie SMK, Vederas JC, Oudit GY. Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases. Biochim Biophys Acta Mol Basis Dis. 2017;1863(8):1942–50. https://doi.org/10.1016/j.bbadis.2016.11.007.

    Article  CAS  PubMed  Google Scholar 

  9. Opatrilova R, Caprnda M, Kubatka P, Valentova V, Uramova S, Nosal V, et al. Adipokines in neurovascular diseases. Biomed Pharmacother. 2018;98:424–32. https://doi.org/10.1016/j.biopha.2017.12.074.

    Article  CAS  PubMed  Google Scholar 

  10. Chu H, Yang X, Huang C, Gao Z, Tang Y, Dong Q. Apelin-13 protects against ischemic blood-brain barrier damage through the effects of aquaporin-4. Cerebrovasc Dis. 2017;44(1–2):10–25. https://doi.org/10.1159/000460261.

    Article  CAS  PubMed  Google Scholar 

  11. Khaksari M, Aboutaleb N, Nasirinezhad F, Vakili A, Madjd Z. Apelin-13 protects the brain against ischemic reperfusion injury and cerebral edema in a transient model of focal cerebral ischemia. J Mol Neurosci. 2012;48(1):201–8. https://doi.org/10.1007/s12031-012-9808-3.

    Article  CAS  PubMed  Google Scholar 

  12. Amani H, Habibey R, Shokri F, Hajmiresmail SJ, Akhavan O, Mashaghi A, et al. Selenium nanoparticles for targeted stroke therapy through modulation of inflammatory and metabolic signaling. Sci Rep. 2019;9(1):6044. https://doi.org/10.1038/s41598-019-42633-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Amani H, Mostafavi E, Alebouyeh MR, Arzaghi H, Akbarzadeh A, Pazoki-Toroudi H, et al. Would colloidal gold nanocarriers present an effective diagnosis or treatment for ischemic stroke? Int J Nanomedicine. 2019;14:8013–31. https://doi.org/10.2147/ijn.s210035.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Stroke--1989. Recommendations on stroke prevention, diagnosis, and therapy. Report of the WHO Task Force on Stroke and other Cerebrovascular Disorders. Stroke. 1989;20(10):1407–31.

  15. Kelly PJ, Albers GW, Chatzikonstantinou A, De Marchis GM, Ferrari J, George P, et al. Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies. Lancet Neurol. 2016;15(12):1238–47. https://doi.org/10.1016/s1474-4422(16)30236-8.

    Article  PubMed  Google Scholar 

  16. Song B, Fang H, Zhao L, Gao Y, Tan S, Lu J, et al. Validation of the ABCD3-I score to predict stroke risk after transient ischemic attack. Stroke. 2013;44(5):1244–8. https://doi.org/10.1161/strokeaha.113.000969.

    Article  CAS  PubMed  Google Scholar 

  17. Song B, Hu R, Pei L, Cao Y, Chen P, Sun S, et al. Dual antiplatelet therapy reduced stroke risk in high-risk patients with transient ischaemic attack assessed by ABCD3-I score. Eur J Neurol. 2019;26(4):610–6. https://doi.org/10.1111/ene.13864.

    Article  CAS  PubMed  Google Scholar 

  18. Hurford R, Li L, Lovett N, Kubiak M, Kuker W, Rothwell PM. Prognostic value of “tissue-based” definitions of TIA and minor stroke: population-based study. Neurology. 2019;92(21):e2455–e61. https://doi.org/10.1212/wnl.0000000000007531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Strambo D, Zambon AA, Roveri L, Giacalone G, Di Maggio G, Peruzzotti-Jametti L, et al. Defining minor symptoms in acute ischemic stroke. Cerebrovasc Dis. 2015;39(3–4):209–15. https://doi.org/10.1159/000375151.

    Article  PubMed  Google Scholar 

  20. Ferrari J, Knoflach M, Kiechl S, Willeit J, Schnabl S, Seyfang L, et al. Early clinical worsening in patients with TIA or minor stroke: the Austrian Stroke Unit Registry. Neurology. 2010;74(2):136–41. https://doi.org/10.1212/WNL.0b013e3181c9188b.

    Article  CAS  PubMed  Google Scholar 

  21. Han Y, Rajah GB, Hussain M, Geng X. Clinical potential of pre-reperfusion hypothermia in ischemic injury. Neurol Res. 2019;41(8):697–703. https://doi.org/10.1080/01616412.2019.1609160.

    Article  PubMed  Google Scholar 

  22. Ran YC, Zhu M, Li SJ, Zhang ZX, Wang X, Zhang Y, et al. Related research and recent progress of ischemic penumbra. World Neurosurg. 2018;116:5–13. https://doi.org/10.1016/j.wneu.2018.04.193.

    Article  PubMed  Google Scholar 

  23. Wu F, Qiu J, Fan Y, Zhang Q, Cheng B, Wu Y, et al. Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating Galphai/Galphaq-CK2 signaling in ischemic stroke. Exp Neurol. 2018;302:136–44. https://doi.org/10.1016/j.expneurol.2018.01.006.

    Article  CAS  PubMed  Google Scholar 

  24. Wu Y, Wang X, Zhou X, Cheng B, Li G, Bai B. Temporal expression of apelin/apelin receptor in ischemic stroke and its therapeutic potential. Front Mol Neurosci. 2017;10:1. https://doi.org/10.3389/fnmol.2017.00001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Aminyavari S, Zahmatkesh M, Farahmandfar M, Khodagholi F, Dargahi L, Zarrindast MR. Protective role of apelin-13 on amyloid beta25-35-induced memory deficit; involvement of autophagy and apoptosis process. Prog Neuro-Psychopharmacol Biol Psychiatry. 2019;89:322–34. https://doi.org/10.1016/j.pnpbp.2018.10.005.

    Article  CAS  Google Scholar 

  26. Chen D, Lee J, Gu X, Wei L, Yu SP. Intranasal delivery of apelin-13 is neuroprotective and promotes angiogenesis after ischemic stroke in mice. ASN Neuro. 2015;7(5). https://doi.org/10.1177/1759091415605114.

  27. Yu M, Yuan HS, Li Q, Li Q, Teng YF. Combination of cells-based therapy with apelin-13 and hyperbaric oxygen efficiently promote neovascularization in ischemic animal model. Eur Rev Med Pharmacol Sci. 2019;23(6):2630–9. https://doi.org/10.26355/eurrev_201903_17413.

    Article  CAS  PubMed  Google Scholar 

  28. Huang C, Dai C, Gong K, Zuo H, Chu H. Apelin-13 protects neurovascular unit against ischemic injuries through the effects of vascular endothelial growth factor. Neuropeptides. 2016;60:67–74. https://doi.org/10.1016/j.npep.2016.08.006.

    Article  CAS  PubMed  Google Scholar 

  29. Fraga-Silva RA, Seeman H, Montecucco F, da Silva AR, Burger F, Costa-Fraga FP, et al. Apelin-13 treatment enhances the stability of atherosclerotic plaques. Eur J Clin Investig. 2018;48(3). https://doi.org/10.1111/eci.12891.

  30. Zhou Y, Wang Y, Qiao S. Apelin: a potential marker of coronary artery stenosis and atherosclerotic plaque stability in ACS patients. Int Heart J. 2014;55(3):204–12.

    Article  CAS  Google Scholar 

  31. Lago F, Dieguez C, Gomez-Reino J, Gualillo O. Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol. 2007;3(12):716–24. https://doi.org/10.1038/ncprheum0674.

    Article  CAS  PubMed  Google Scholar 

  32. Xin Q, Cheng B, Pan Y, Liu H, Yang C, Chen J, et al. Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation. Peptides. 2015;63:55–62. https://doi.org/10.1016/j.peptides.2014.09.016.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank all the participants of the study and acknowledge the contribution from Jian Chai in statistical analysis.

Funding

This study was funded by the National Natural Science Foundation of China (81571158) and the Education Department of Henan Province (16A320054).

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Author notes

  1. Xiao Wang and Xuan Tian contributed equally to the manuscript (co-first authors)

Authors and Affiliations

  1. Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou, 450052, Henan, China

    Xiao Wang, Xuan Tian, Lu-lu Pei, Peng-peng Niu, Yinan Guo, Ruiyao Hu, Kai Liu, Mengke Tian, Youfeng Li, Chunhui Wang, Xin Wang, Yuming Xu & Bo Song

  2. Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou, 450052, China

    Xiao Wang, Xuan Tian, Lu-lu Pei, Peng-peng Niu, Yinan Guo, Ruiyao Hu, Kai Liu, Mengke Tian, Youfeng Li, Chunhui Wang, Xin Wang, Yuming Xu & Bo Song

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  1. Xiao Wang
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Correspondence to Yuming Xu or Bo Song.

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Wang, X., Tian, X., Pei, Ll. et al. The Association Between Serum Apelin-13 and the Prognosis of Acute Ischemic Stroke. Transl. Stroke Res. 11, 700–707 (2020). https://doi.org/10.1007/s12975-019-00769-w

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