{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:07:43Z","timestamp":1780337263185,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Growth differentiation factor-15 (GDF-15) is a protein that belongs to the transforming growth factor beta superfamily and has been found elevated in cases of organ injury such as liver, kidney, heart, and lung, as well as cardiovascular diseases and cancer. Soluble urokinase plasminogen activator receptor (suPAR) is a protein which is expressed mainly on immune cells and endothelial and smooth muscle cells, and is a marker of severity and intensity of inflammation in acute and chronic diseases. The aim of the present study was to compare GDF-15 serum levels between patients with acute cerebrovascular incidents and healthy controls and to investigate the possible correlation of GDF-15 serum levels and inflammatory markers, such as serum C-reactive protein (CRP) and plasma suPAR, in the above-mentioned groups. Methods: This is a retrospective study. Thirty-one patients were included in the study, with a mean age \u00b1 SD of 67 \u00b1 13 years, compared to 18 age-matched healthy controls. Results: In the patient group a statistically significant positive correlation of serum levels of GDF15 values with suPAR and CRP emerged (rs = 0.516, p = 0.003) and (rs = 0.409, p = 0.022), respectively, and no significant correlation was found in the group of controls (rs = 0.271, p = 0.277) and (rs = 0.423, p = 0.080), respectively. Conclusions: These findings support the role of inflammation as a key underlying mechanism in acute cerebrovascular injury and suggest that GDF-15 may serve as a valuable adjunct biomarker for assessing disease severity and inflammatory burden.<\/jats:p>","DOI":"10.3390\/jpm16060300","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:11:01Z","timestamp":1780333861000},"page":"300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GDF-15: Can It Be Used as a Biomarker in Acute Cerebrovascular Incidents?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4844-2712","authenticated-orcid":false,"given":"Areti","family":"Kourti","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Keskilidou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Skoura","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi","family":"Karalazou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Thisiadou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-7480","authenticated-orcid":false,"given":"Kali","family":"Makedou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liuiz\u0117 Abramavi\u010di\u016bt\u0117, A., and Mongirdien\u0117, A. (2024). TGF-\u03b2 Isoforms and GDF-15 in the Development and Progression of Atherosclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042104"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1002\/ejhf.2887","article-title":"Incremental prognostic value of biomarkers in PARADIGM-HF","volume":"25","author":"McDowell","year":"2023","journal-title":"Eur. J. Heart Fail."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"bnaa007","DOI":"10.1210\/endrev\/bnaa007","article-title":"GDF15: A Hormone Conveying Somatic Distress to the Brain","volume":"1","author":"Lockhart","year":"2020","journal-title":"Endocr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s10741-021-10105-w","article-title":"Biomarkers for the diagnosis and management of heart failure","volume":"27","author":"Castiglione","year":"2022","journal-title":"Heart Fail. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/cne.1333","article-title":"Expression of growth differentiation factor-15\/ macrophage inhibitory cytokine-1 (GDF-15\/MIC-1) in the perinatal, adult, and injured rat brain","volume":"439","author":"Schober","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/ACO.0000000000001532","article-title":"Biomarkers of acute brain injury","volume":"38","author":"Prus","year":"2025","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrm2821","article-title":"Regulation of cell signalling by uPAR","volume":"11","author":"Smith","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rasmussen, L.J.H., Petersen, J.E.V., and Eugen-Olsen, J. (2021). Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.780641"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.clinbiochem.2019.05.010","article-title":"Analytical, biochemical and clearance considerations of soluble urokinase plasminogen activator receptor (suPAR) in healthy individuals","volume":"69","author":"Appleby","year":"2019","journal-title":"Clin. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nm.4242","article-title":"Bone marrow-derived immature myeloid cells are a main source of circulating suPAR contributing to proteinuric kidney disease","volume":"23","author":"Hahm","year":"2017","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.cca.2015.02.031","article-title":"Soluble urokinase plasminogen activator receptor\u2014A valuable biomarker in systemic lupus erythematosus?","volume":"444","author":"Enocsson","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_12","first-page":"658","article-title":"Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in non-alcoholic fatty liver disease","volume":"165","author":"Martinsson","year":"2014","journal-title":"Transl. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15462","DOI":"10.1038\/s41598-020-72377-w","article-title":"Soluble urokinase plasminogen activator receptor level in individuals of advanced age","volume":"10","author":"Wlazel","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Silva-Bermudez, L.S., Kl\u00fcter, H., and Kzhyshkowska, J.G. (2024). Macrophages as a Source and Target of GDF-15. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202405.1794.v1"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3796","DOI":"10.1172\/JCI91561","article-title":"NF-\u03baB regulates GDF-15 to suppress macrophage surveillance during early tumor development","volume":"127","author":"Ratnam","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1182\/blood-2011-03-341776","article-title":"Regulation of hepcidin expression at high altitude","volume":"119","author":"Talbot","year":"2012","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1111\/j.1474-9726.2010.00629.x","article-title":"Macrophage inhibitory cytokine-1 (MIC-1\/GDF15): A new marker of all-cause mortality","volume":"9","author":"Wiklund","year":"2010","journal-title":"Aging Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/S0140-6736(16)31276-4","article-title":"Early invasive versus noninvasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised multicentre study","volume":"388","author":"Wallentin","year":"2016","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1161\/CIRCULATIONAHA.109.928846","article-title":"Serial measurement of growthdifferentiation factor-15 in heart failure: Relation to disease severity and prognosis in the Valsartan Heart Failure Trial","volume":"122","author":"Anand","year":"2010","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.resuscitation.2020.05.001","article-title":"GDF-15 is associated with sudden cardiac death due to incident myocardial infarction","volume":"152","author":"Andersson","year":"2020","journal-title":"Resuscitation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1161\/ATVBAHA.110.213512","article-title":"Growth differentation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome. Observations from PROVE IT-TIMI 22","volume":"31","author":"Bonaca","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1016\/S0140-6736(16)00741-8","article-title":"The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: A derivation and validation study","volume":"387","author":"Hijazi","year":"2016","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cort\u00e9s, M., Lumpuy-Castillo, J., Garc\u00eda-Talavera, C.S., Rivera, M.B.A., de Miguel, L., Bollas, A.J., Romero-Otero, J.M., Chapel, J.A.E., Taibo-Urqu\u00eda, M., and Pello, A.M. (2025). New Biomarkers in the Prognostic Assessment of Acute Heart Failure with Reduced Ejection Fraction: Beyond Natriuretic Peptides. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26030986"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13148-024-01734-7","article-title":"DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain","volume":"16","author":"Gadd","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1161\/STROKEAHA.118.022207","article-title":"Ischemic Stroke Increases Heart Vulnerability to Ischemia-Reperfusion and Alters Myocardial Cardioprotective Pathways","volume":"49","author":"Meloux","year":"2018","journal-title":"Stroke"},{"key":"ref_27","first-page":"11","article-title":"Emerging biomarkers in ischemic stroke","volume":"9","author":"Lee","year":"2025","journal-title":"Vessel. Plus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"72","DOI":"10.5582\/bst.2024.01305","article-title":"Growth and differentiation factor 15: An emerging therapeutic target for brain diseases","volume":"19","author":"Zhou","year":"2025","journal-title":"Biosci. Trends"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39481","DOI":"10.1038\/srep39481","article-title":"Serum Soluble Urokinase Type Plasminogen Activator Receptor as a Biological Marker of Bacterial Infection in Adults: A Systematic Review and Meta-Analysis","volume":"6","author":"Ni","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/10408363.2016.1269310","article-title":"The Intriguing Role of Soluble Urokinase Receptor in Inflammatory Diseases","volume":"54","author":"Desmedt","year":"2017","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.bbi.2021.08.224","article-title":"suPAR: A Newer Biomarker of Systemic Chronic Inflammation","volume":"98","author":"Marsland","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1007\/s10753-024-02185-1","article-title":"Soluble Urokinase-Type Plasminogen Activator Receptor and Inflammatory Biomarker Response with Prognostic Significance after Acute Neuronal Injury\u2014A Prospective Cohort Study","volume":"48","author":"Sajanti","year":"2025","journal-title":"Inflammation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"155324","DOI":"10.1016\/j.cyto.2020.155324","article-title":"Elevated Cytokine, Chemokine, and Growth and differentiation Factor-15 Levels in Hemorrhagic Shock and Encephalopathy Syndrome: A Retrospective Observational Study","volume":"137","author":"Yamaguchi","year":"2021","journal-title":"Cytokine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.braindev.2021.10.003","article-title":"Growth and Differentiation Factor-15 as a Potential Prognostic Biomarker for Status-Epilepticus-Associated-With-Fever: A Pilot Study","volume":"44","author":"Yamaguchi","year":"2022","journal-title":"Brain Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1111\/head.14618","article-title":"Mitochondrial Metabolism Related Markers GDF-15, FGF-21, and HIF-1\u03b1Are Elevated in Pediatric Migraine Attacks","volume":"63","author":"Kilinc","year":"2023","journal-title":"Headache"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"M\u00e9loux, A., Dogon, G., Rigal, E., Rochette, L., Bejot, Y., and Vergely, C. (2024). Proximal and distant expression of growth differentiation factor 15 (GDF15) correlate with neurological deficit following experimental ischemic stroke. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0307105"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1002\/ehf2.14484","article-title":"GDF-15 at admission predicts cardiovascular death, heart failure, and bleeding outcomes in patients with CAD","volume":"10","author":"Wang","year":"2023","journal-title":"ESC Heart Fail."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/6\/300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:21:57Z","timestamp":1780334517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/6\/300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["jpm16060300"],"URL":"https:\/\/doi.org\/10.3390\/jpm16060300","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]}}}