{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:40:55Z","timestamp":1760060455779,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002711","name":"Kirsehir Ahi Evran University","doi-asserted-by":"publisher","award":["TIP.A2.24.007"],"award-info":[{"award-number":["TIP.A2.24.007"]}],"id":[{"id":"10.13039\/501100002711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Multiple sclerosis (MS) is an immune-mediated neuroinflammatory disorder with a multifactorial etiology involving genetic susceptibility, environmental triggers, and vascular contributions. Carotid intima\u2013media thickness (CIMT) is a significant marker of endothelial dysfunction. Endothelial cell-specific molecule-1 (endocan) and hyaluronic acid, key components implicated in endothelial and vascular remodeling, may significantly contribute to the inflammatory and vascular pathologies observed in MS. We aimed to investigate the relationship between CIMT and endothelial biomarkers, such as endocan and hyaluronic acid, in patients with MS. Methods: In this cross-sectional study, 100 patients with relapsing\u2013remitting MS and 56 healthy controls were included. Demographic, clinical, laboratory, and imaging data were documented. CIMT was measured bilaterally using high-resolution B-mode ultrasonography. Serum endocan and hyaluronic acid levels were quantified via enzyme-linked immunosorbent assays. Results: MS patients exhibited significantly higher CIMT and serum endocan levels compared with controls (p &lt; 0.001). CIMT values were significantly elevated in MS patients, with longer disease duration, higher expanded disability status scale scores, and an older diagnosis age (p &lt; 0.05). However, serum endocan and hyaluronic acid levels did not significantly differ between MS subgroups based on disease duration, disability severity, and diagnosis age. Additionally, there was no correlation between CIMT and serum endocan and hyaluronic acid levels in MS patients (p &gt; 0.05). Conclusions: Increased CIMT and serum endocan levels in MS patients may indicate endothelial dysfunction suggesting vascular involvement in MS. The lack of a correlation between CIMT and endocan and hyaluronic acid levels reveals the complexity of vascular and immune interactions in MS, which needs further research.<\/jats:p>","DOI":"10.3390\/life15091388","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T13:27:44Z","timestamp":1756733264000},"page":"1388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Relationship Between Carotid Intima\u2013Media Thickness, Serum Endocan and Hyaluronic Acid Levels in Multiple Sclerosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7553-2034","authenticated-orcid":false,"given":"Selcen","family":"Duran","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir 40100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2367-1128","authenticated-orcid":false,"given":"Asuman","family":"Celikbilek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sincan Training and Research Hospital, Ankara 06949, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-5469","authenticated-orcid":false,"given":"Ahmet Said","family":"Cil","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir 40100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7614-281X","authenticated-orcid":false,"given":"Bilal","family":"Ilanbey","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir 40100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8002-6208","authenticated-orcid":false,"given":"Aydan","family":"Koysuren","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir 40100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burc Esra","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir 40100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"ref_1","first-page":"14","article-title":"Multiple sclerosis: 2024 update","volume":"6","author":"Klotz","year":"2025","journal-title":"Free Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105902","DOI":"10.1016\/j.msard.2024.105902","article-title":"Vascular function in multiple sclerosis: Systematic review with meta-analysis","volume":"91","author":"Zheng","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple sclerosis\u2014A review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.pathophys.2010.04.002","article-title":"Multiple sclerosis and cerebral endothelial dysfunction: Mechanisms","volume":"18","author":"Alexander","year":"2011","journal-title":"Pathophysiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11940-024-00816-4","article-title":"A hypoxia-inflammation cycle and multiple sclerosis: Mechanisms and therapeutic implications","volume":"27","author":"Soroush","year":"2025","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_6","first-page":"746","article-title":"Vascular disease in patients with multiple sclerosis: A review","volume":"4","author":"Caprio","year":"2016","journal-title":"J. Vasc. Med. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.neurad.2019.10.002","article-title":"Is multiple sclerosis a risk factor for atherosclerosis?","volume":"48","author":"Yuksel","year":"2021","journal-title":"J. Neuroradiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Najmi, E.A., Mirzaasgari, Z., Motamed, M.R., and Aslani, A. (2024). Carotid intima-media thickness and risk of atherosclerosis in multiple sclerosis: A cross-sectional study. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0314031"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.14366\/usg.22053","article-title":"Biomechanical changes of the common carotid artery and internal jugular vein in patients with multiple sclerosis","volume":"42","author":"Rastegari","year":"2023","journal-title":"Ultrasonography"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103348","DOI":"10.1016\/j.amsu.2022.103348","article-title":"Carotid intima-media thickness measurements in patients with multiple sclerosis","volume":"75","author":"Farzan","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"579","DOI":"10.4103\/0253-7613.144891","article-title":"Endocan: A novel circulating proteoglycan","volume":"46","author":"Kali","year":"2014","journal-title":"Indian J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1177\/0003319720903586","article-title":"Novel Biomarkers for Evaluation of Endothelial Dysfunction","volume":"71","author":"Leite","year":"2020","journal-title":"Angiology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, S., Bai, T., and Feng, J. (2024). Endocan, a novel glycoprotein with multiple biological activities, may play important roles in neurological diseases. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1438367"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1159\/000025758","article-title":"Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies","volume":"37","author":"Bechard","year":"2000","journal-title":"J. Vasc. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3109\/10520295.2011.577754","article-title":"Expression and distribution of endocan in human tissues","volume":"87","author":"Zhang","year":"2012","journal-title":"Biotech. Histochem."},{"key":"ref_16","first-page":"4091","article-title":"Serum endocan levels in multiple sclerosis relapse and remission","volume":"25","author":"Akil","year":"2021","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.4274\/tnd.2021.81073","article-title":"Could Serum Endocan Be a Vascular Endothelial Marker in Relapsing-Remitting Multiple Sclerosis?","volume":"27","author":"Atalar","year":"2021","journal-title":"Turk. J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Valachov\u00e1, K., Hassan, M.E., and \u0160olt\u00e9s, L. (2024). Hyaluronan: Sources, Structure, Features and Applications. Molecules, 29.","DOI":"10.3390\/molecules29030739"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/1742-2094-11-101","article-title":"Association between plasma levels of hyaluronic acid and functional outcome in acute stroke patients","volume":"11","author":"Tang","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sullivan, R.C., Rockstrom, M.D., Schmidt, E.P., and Hippensteel, J.A. (2021). Endothelial glycocalyx degradation during sepsis: Causes and consequences. Matrix Biol. Plus, 12.","DOI":"10.1016\/j.mbplus.2021.100094"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e70545","DOI":"10.1111\/cns.70545","article-title":"Endothelial Glycocalyx in Cerebral Infarction After Endovascular Treatment in Patients With Intracranial Artery Stenosis","volume":"31","author":"Zhao","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1016\/j.jss.2011.09.025","article-title":"The role of hyaluronic acid in atherosclerosis and intimal hyperplasia","volume":"173","author":"Sadowitz","year":"2012","journal-title":"J. Surg. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103763","DOI":"10.1016\/j.isci.2022.103763","article-title":"A TLR\/CD44 axis regulates T cell trafficking in experimental and human multiple sclerosis","volume":"25","author":"Tredicine","year":"2022","journal-title":"iScience"},{"key":"ref_24","first-page":"1599","article-title":"A novel marker relationship between carotid intima media thickness and disease activity score-28 in patients with rheumatoid arthritis: Human endothelial cell-specific molecule-1","volume":"49","author":"Tuzcu","year":"2019","journal-title":"Turk. J. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1177\/0003319715616240","article-title":"Endocan Levels and Subclinical Atherosclerosis in Patients With Systemic Lupus Erythematosus","volume":"67","author":"Icli","year":"2016","journal-title":"Angiology"},{"key":"ref_26","first-page":"129","article-title":"Assessment of Endocan Serum Level in Patients with Beh\u00e7et Disease: Relation to Disease Activity and Carotid Intima Media Thickness","volume":"27","author":"Hassan","year":"2020","journal-title":"Egypt. J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cashion, J.M., Young, K.M., and Sutherland, B.A. (2023). How does neurovascular unit dysfunction contribute to multiple sclerosis?. Neurobiol. Dis., 178.","DOI":"10.1016\/j.nbd.2023.106028"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105660","DOI":"10.1016\/j.msard.2024.105660","article-title":"Carotid intima media thickness in multiple sclerosis: A CLSA study","volume":"87","author":"Marrie","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105752","DOI":"10.1016\/j.msard.2024.105752","article-title":"Carotid intima media thickness and multiple sclerosis","volume":"89","author":"Saleh","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S1474-4422(23)00377-0","article-title":"Blood-brain barrier dysfunction in multiple sclerosis: Causes, consequences, and potential effects of therapies","volume":"23","author":"Zierfuss","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1039\/D4MH01598C","article-title":"Hyaluronic acid-based hydrogels modulate neuroinflammation and extracellular matrix remodelling in multiple sclerosis: Insights from a primary cortical cell model","volume":"12","author":"Bagnoli","year":"2025","journal-title":"Mater. Horiz."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Pei, S., Zhou, Z., Wang, Z., Peng, Y., Chen, J., and Wang, H. (2021). High level of serum and cerebrospinal fluid of heparan sulfate and hyaluronic acid might be a biomarker of severity of neuromyelitis optica. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.705536"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nagy, N., Kuipers, H.F., Marshall, P.L., Wang, E., Kaber, G., and Bollyky, P.L. (2018). Hyaluronan in Autoimmunity and Immune Dysregulation. Matrix Biol. J. Int. Soc. Matrix Biol., 78.","DOI":"10.1016\/j.matbio.2018.03.022"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/9\/1388\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:37:20Z","timestamp":1760035040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/9\/1388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":34,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["life15091388"],"URL":"https:\/\/doi.org\/10.3390\/life15091388","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,9,1]]}}}