{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:47:47Z","timestamp":1791478067716,"version":"4.3.4"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005758","name":"Universit\u00e0 Politecnica delle Marche","doi-asserted-by":"publisher","award":["RSA Grant"],"award-info":[{"award-number":["RSA Grant"]}],"id":[{"id":"10.13039\/501100005758","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetol Metab Syndr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endothelial cellular senescence is emerging as a key mechanism of age-related vascular dysfunction. Disruption of the endothelium glycocalyx and shedding of the syndecan (SDC) ectodomains have been associated with several age-related diseases. Although SDC4 is highly expressed in endothelial cells, its levels and shedding in senescent endothelial cells and vascular endothelial dysfunction associated with aging are still unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To assess whether SDC4 expression was affected by inflammatory conditions, we evaluated its levels in young human umbilical vein endothelial cells (HUVECs) treated with TNF-\u03b1 at a concentration of 50\u00a0ng\/mL for 24\u00a0h and in cells undergoing replicative senescence. Plasma levels of SDC4 were evaluated in two previously recruited cohorts of (i) subjects with type 2 diabetes (T2D, n\u2009=\u2009110) followed for a median of 16.8\u00a0years and age- and gender-matched healthy subjects (n\u2009=\u2009100), and (ii) middle-aged subjects with mild-to-moderate dyslipidemia. Binomial logistic regression was used to assess whether SDC4 levels could be prognostic for major adverse cardiovascular events (MACE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the in vitro study, we showed that HUVECs, when exposed to TNF-\u03b1 or undergoing replicative senescence, exhibited elevated expression levels of SDC4 and matrix metallopeptidase 9 (MMP-9), as well as increased shedding of SDC4 into the extracellular microenvironment, in comparison to actively proliferating young HUVECs.<\/jats:p>\n                    <jats:p>Analysis of human samples revealed that patients with T2D without complications exhibited higher SDC4 levels compared to healthy controls and those with T2D vascular complications. In particular, patients with a history of major adverse cardiovascular events (MACE) had lower SDC4 levels. The longitudinal evaluation revealed that higher SDC4 levels predict the onset of new MACE during a 16.8-year follow-up. In the second cohort, no significant association was observed between SDC4 and endothelial dysfunction, assessed by flow-mediated dilation (FMD) or nitric oxide metabolites. SDC4 levels correlated positively with C-reactive protein (CRP) in both cohorts and with PAI-1 in the cohort of patients with T2D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, we conclude that the shedding of SDC4 from endothelial cells increases under acute (TNF-\u03b1 treatment) and chronic (senescence) inflammatory conditions and that increased circulating SDC4 levels are associated with systemic inflammation in pathological aging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13098-024-01431-8","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:02:12Z","timestamp":1724112132000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Syndecan 4 is a marker of endothelial inflammation in pathological aging and predicts long-term cardiovascular outcomes in type 2 diabetes"],"prefix":"10.1186","volume":"16","author":[{"given":"Angelica","family":"Giuliani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Ramini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Sbriscia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolina","family":"Crocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Tiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rita","family":"Rippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Bonfigli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Sabbatinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"1431_CR1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.ejvs.2004.12.019","volume":"29","author":"TA Alam","year":"2005","unstructured":"Alam TA, Seifalian AM, Baker D. A review of methods currently used for assessment of in vivo endothelial function. Eur J Vasc Endovasc Surg. 2005;29:269\u201376.","journal-title":"Eur J Vasc Endovasc Surg"},{"key":"1431_CR2","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.2337\/dc22-S002","volume":"45","author":"American Diabetes Association Professional Practice","year":"2022","unstructured":"American Diabetes Association Professional Practice. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45:S17\u201338.","journal-title":"Diabetes Care"},{"key":"1431_CR3","doi-asserted-by":"publisher","first-page":"17308","DOI":"10.1073\/pnas.1413725111","volume":"111","author":"N Baeyens","year":"2014","unstructured":"Baeyens N, Mulligan-Kehoe MJ, Corti F, Simon DD, Ross TD, Rhodes JM, Wang TZ, Mejean CO, Simons M, Humphrey J, Schwartz MA. Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proc Natl Acad Sci U S A. 2014;111:17308\u201313.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1431_CR4","doi-asserted-by":"publisher","first-page":"50835","DOI":"10.18632\/oncotarget.10615","volume":"7","author":"AR Bonfigli","year":"2016","unstructured":"Bonfigli AR, Spazzafumo L, Prattichizzo F, Bonafe M, Mensa E, Micolucci L, Giuliani A, Fabbietti P, Testa R, Boemi M, Lattanzio F, Olivieri F. Leukocyte telomere length and mortality risk in patients with type 2 diabetes. Oncotarget. 2016;7:50835\u201344.","journal-title":"Oncotarget"},{"key":"1431_CR5","doi-asserted-by":"publisher","first-page":"4911","DOI":"10.1021\/acs.nanolett.1c00064","volume":"21","author":"N Chala","year":"2021","unstructured":"Chala N, Moimas S, Giampietro C, Zhang X, Zambelli T, Exarchos V, Nazari-Shafti TZ, Poulikakos D, Ferrari A. Mechanical fingerprint of senescence in endothelial cells. Nano Lett. 2021;21:4911\u201320.","journal-title":"Nano Lett"},{"key":"1431_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.542567","volume":"7","author":"PY Chia","year":"2020","unstructured":"Chia PY, Teo A, Yeo TW. Overview of the assessment of endothelial function in humans. Front Med. 2020;7: 542567.","journal-title":"Front Med"},{"issue":"3","key":"1431_CR7","doi-asserted-by":"publisher","first-page":"342","DOI":"10.3390\/biom11030342","volume":"11","author":"M De Luca","year":"2021","unstructured":"De Luca M, Bryan DR, Hunter GR. Circulating levels of the heparan sulfate proteoglycan syndecan-4 positively associate with blood pressure in healthy premenopausal women. Biomolecules. 2021;11(3):342.","journal-title":"Biomolecules."},{"key":"1431_CR8","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.1007\/s40520-022-02210-z","volume":"34","author":"M De Luca","year":"2022","unstructured":"De Luca M, Bryan DR, Hunter GR. Serum syndecan-4 correlates with blood pressure and cardiovascular parameters but not proinflammatory markers in healthy older women. Aging Clin Exp Res. 2022;34:2541\u20135.","journal-title":"Aging Clin Exp Res"},{"key":"1431_CR9","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1161\/ATVBAHA.121.315941","volume":"41","author":"G De Rossi","year":"2021","unstructured":"De Rossi G, Vahatupa M, Cristante E, Arokiasamy S, Liyanage SE, May U, Pellinen L, Uusitalo-Jarvinen H, Bainbridge JW, Jarvinen TAH, Whiteford JR. Pathological angiogenesis requires syndecan-4 for efficient VEGFA-induced VE-cadherin internalization. Arterioscler Thromb Vasc Biol. 2021;41:1374\u201389.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"1431_CR10","doi-asserted-by":"publisher","first-page":"R9","DOI":"10.1172\/JCI10559","volume":"107","author":"F Echtermeyer","year":"2001","unstructured":"Echtermeyer F, Streit M, Wilcox-Adelman S, Saoncella S, Denhez F, Detmar M, Goetinck P. Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4. J Clin Invest. 2001;107:R9\u201314.","journal-title":"J Clin Invest"},{"key":"1431_CR11","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12890-016-0267-4","volume":"16","author":"S Esposito","year":"2016","unstructured":"Esposito S, Bianchini S, Gambino M, Madini B, Di Pietro G, Umbrello G, Presicce ML, Ruggiero L, Terranova L, Principi N. Measurement of lipocalin-2 and syndecan-4 levels to differentiate bacterial from viral infection in children with community-acquired pneumonia. BMC Pulm Med. 2016;16:103.","journal-title":"BMC Pulm Med"},{"key":"1431_CR12","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1369\/0022155417740881","volume":"66","author":"BL Farrugia","year":"2018","unstructured":"Farrugia BL, Lord MS, Melrose J, Whitelock JM. The role of heparan sulfate in inflammation, and the development of biomimetics as anti-inflammatory strategies. J Histochem Cytochem. 2018;66:321\u201336.","journal-title":"J Histochem Cytochem"},{"key":"1431_CR13","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.1002\/cphy.c210029","volume":"12","author":"CA Foote","year":"2022","unstructured":"Foote CA, Soares RN, Ramirez-Perez FI, Ghiarone T, Aroor A, Manrique-Acevedo C, Padilla J, Martinez-Lemus L. Endothelial glycocalyx. Compr Physiol. 2022;12:3781\u2013811.","journal-title":"Compr Physiol"},{"key":"1431_CR14","doi-asserted-by":"publisher","first-page":"738","DOI":"10.3390\/toxins13100738","volume":"13","author":"F Guerrero","year":"2021","unstructured":"Guerrero F, Carmona A, Jimenez MJ, Obrero T, Pulido V, Moreno JA, Soriano S, Martin-Malo A, Aljama P. Passage number-induced replicative senescence modulates the endothelial cell response to protein-bound uremic toxins. Toxins. 2021;13:738.","journal-title":"Toxins"},{"key":"1431_CR15","first-page":"183","volume":"1","author":"HA Hadi","year":"2005","unstructured":"Hadi HA, Carr CS, Al Suwaidi J. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005;1:183\u201398.","journal-title":"Vasc Health Risk Manag"},{"key":"1431_CR16","doi-asserted-by":"publisher","first-page":"435","DOI":"10.14348\/molcells.2014.0078","volume":"37","author":"KS Heo","year":"2014","unstructured":"Heo KS, Fujiwara K, Abe J. Shear stress and atherosclerosis. Mol Cells. 2014;37:435\u201340.","journal-title":"Mol Cells"},{"key":"1431_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163532","volume":"11","author":"AJ Jaroszynski","year":"2016","unstructured":"Jaroszynski AJ, Jaroszynska A, Przywara S, Zaborowski T, Ksiazek A, Dabrowski W. Syndecan-4 Is an independent predictor of all-cause as well as cardiovascular mortality in hemodialysis patients. PLoS ONE. 2016;11: e0163532.","journal-title":"PLoS ONE"},{"key":"1431_CR18","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1177\/0003319720903586","volume":"71","author":"AR Leite","year":"2020","unstructured":"Leite AR, Borges-Canha M, Cardoso R, Neves JS, Castro-Ferreira R, Leite-Moreira A. Novel biomarkers for evaluation of endothelial dysfunction. Angiology. 2020;71:397\u2013410.","journal-title":"Angiology"},{"key":"1431_CR19","doi-asserted-by":"publisher","first-page":"H571","DOI":"10.1152\/ajpheart.00038.2018","volume":"315","author":"Y Li","year":"2018","unstructured":"Li Y, Peng Z, Wang C, Li L, Leng Y, Chen R, Yuan H, Zhou S, Zhang Z, Chen AF. Novel role of PKR in palmitate-induced Sirt1 inactivation and endothelial cell senescence. Am J Physiol Heart Circ Physiol. 2018;315:H571\u201380.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"1431_CR20","doi-asserted-by":"publisher","first-page":"3051","DOI":"10.3390\/jcm9093051","volume":"9","author":"M Lipphardt","year":"2020","unstructured":"Lipphardt M, Dihazi H, Maas JH, Schafer AK, Amlaz SI, Ratliff BB, Koziolek MJ, Wallbach M. Syndecan-4 as a marker of endothelial dysfunction in patients with resistant hypertension. J Clin Med. 2020;9:3051.","journal-title":"J Clin Med."},{"key":"1431_CR21","doi-asserted-by":"publisher","first-page":"H531","DOI":"10.1152\/ajpheart.00104.2018","volume":"315","author":"DR Machin","year":"2018","unstructured":"Machin DR, Bloom SI, Campbell RA, Phuong TTT, Gates PE, Lesniewski LA, Rondina MT, Donato AJ. Advanced age results in a diminished endothelial glycocalyx. Am J Physiol Heart Circ Physiol. 2018;315:H531\u20139.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"1431_CR22","doi-asserted-by":"publisher","first-page":"2320","DOI":"10.1111\/febs.12174","volume":"280","author":"T Manon-Jensen","year":"2013","unstructured":"Manon-Jensen T, Multhaupt HA, Couchman JR. Mapping of matrix metalloproteinase cleavage sites on syndecan-1 and syndecan-4 ectodomains. FEBS J. 2013;280:2320\u201331.","journal-title":"FEBS J"},{"key":"1431_CR23","doi-asserted-by":"publisher","first-page":"2005970","DOI":"10.1371\/journal.pbio.2005970","volume":"16","author":"C McQuin","year":"2018","unstructured":"McQuin C, Goodman A, Chernyshev V, Kamentsky L, Cimini BA, Karhohs KW, Doan M, Ding L, Rafelski SM, Thirstrup D, Wiegraebe W, Singh S, Becker T, Caicedo JC, Carpenter AE. Cell profiler 3.0: next-generation image processing for biology. PLoS Biol. 2018;16:2005970.","journal-title":"PLoS Biol."},{"key":"1431_CR24","doi-asserted-by":"publisher","first-page":"1725285","DOI":"10.1080\/20013078.2020.1725285","volume":"9","author":"E Mensa","year":"2020","unstructured":"Mensa E, Guescini M, Giuliani A, Bacalini MG, Ramini D, Corleone G, Ferracin M, Fulgenzi G, Graciotti L, Prattichizzo F, Sorci L, Battistelli M, Monsurro V, Bonfigli AR, Cardelli M, Recchioni R, Marcheselli F, Latini S, Maggio S, Fanelli M, Amatori S, Storci G, Ceriello A, Stocchi V, De Luca M, Magnani L, Rippo MR, Procopio AD, Sala C, Budimir I, Bassi C, Negrini M, Garagnani P, Franceschi C, Sabbatinelli J, Bonafe M, Olivieri F. Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells. J Extracell Vesicles. 2020;9:1725285.","journal-title":"J Extracell Vesicles"},{"key":"1431_CR25","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1006\/niox.2000.0319","volume":"5","author":"KM Miranda","year":"2001","unstructured":"Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5:62\u201371.","journal-title":"Nitric Oxide"},{"key":"1431_CR26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3389\/fcell.2020.00253","volume":"8","author":"L Mockl","year":"2020","unstructured":"Mockl L. The emerging role of the mammalian glycocalyx in functional membrane organization and immune system regulation. Front Cell Dev Biol. 2020;8:253.","journal-title":"Front Cell Dev Biol"},{"key":"1431_CR27","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1093\/jb\/mvt024","volume":"154","author":"E Okuyama","year":"2013","unstructured":"Okuyama E, Suzuki A, Murata M, Ando Y, Kato I, Takagi Y, Takagi A, Murate T, Saito H, Kojima T. Molecular mechanisms of syndecan-4 upregulation by TNF-alpha in the endothelium-like EAhy926 cells. J Biochem. 2013;154:41\u201350.","journal-title":"J Biochem"},{"key":"1431_CR28","doi-asserted-by":"publisher","first-page":"9076485","DOI":"10.1155\/2018\/9076485","volume":"2018","author":"F Olivieri","year":"2018","unstructured":"Olivieri F, Prattichizzo F, Grillari J, Balistreri CR. Cellular senescence and inflammaging in age-related diseases. Mediators Inflamm. 2018;2018:9076485.","journal-title":"Mediators Inflamm"},{"key":"1431_CR29","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.2337\/db14-1820","volume":"64","author":"AK Palmer","year":"2015","unstructured":"Palmer AK, Tchkonia T, LeBrasseur NK, Chini EN, Xu M, Kirkland JL. Cellular Senescence in type 2 diabetes: a therapeutic opportunity. Diabetes. 2015;64:2289\u201398.","journal-title":"Diabetes"},{"key":"1431_CR30","doi-asserted-by":"publisher","first-page":"240","DOI":"10.2337\/db20-0199","volume":"70","author":"F Prattichizzo","year":"2021","unstructured":"Prattichizzo F, De Nigris V, Sabbatinelli J, Giuliani A, Castano C, Parrizas M, Crespo I, Grimaldi A, Baranzini N, Spiga R, Mancuso E, Rippo MR, Procopio AD, Novials A, Bonfigli AR, Garavelli S, La Sala L, Matarese G, de Candia P, Olivieri F, Ceriello A. CD31(+) Extracellular vesicles from patients with type 2 diabetes shuttle a miRNA signature associated with cardiovascular complications. Diabetes. 2021;70:240\u201354.","journal-title":"Diabetes"},{"key":"1431_CR31","doi-asserted-by":"publisher","first-page":"4686","DOI":"10.1096\/fj.14-252221","volume":"28","author":"R Ramnath","year":"2014","unstructured":"Ramnath R, Foster RR, Qiu Y, Cope G, Butler MJ, Salmon AH, Mathieson PW, Coward RJ, Welsh GI, Satchell SC. Matrix metalloproteinase 9-mediated shedding of syndecan 4 in response to tumor necrosis factor alpha: a contributor to endothelial cell glycocalyx dysfunction. FASEB J. 2014;28:4686\u201399.","journal-title":"FASEB J"},{"key":"1431_CR32","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.kint.2019.09.035","volume":"97","author":"RD Ramnath","year":"2020","unstructured":"Ramnath RD, Butler MJ, Newman G, Desideri S, Russell A, Lay AC, Neal CR, Qiu Y, Fawaz S, Onions KL, Gamez M, Crompton M, Michie C, Finch N, Coward RJ, Welsh GI, Foster RR, Satchell SC. Blocking matrix metalloproteinase-mediated syndecan-4 shedding restores the endothelial glycocalyx and glomerular filtration barrier function in early diabetic kidney disease. Kidney Int. 2020;97:951\u201365.","journal-title":"Kidney Int"},{"key":"1431_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-022-01535-3","author":"J Sabbatinelli","year":"2022","unstructured":"Sabbatinelli J, Castiglione S, Macr\u00ec F, Giuliani A, Ramini D, Vinci MC, Tortato E, Bonfigli AR, Olivieri F, Raucci A. Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study. Cardiovasc Diabetol. 2022. https:\/\/doi.org\/10.1186\/s12933-022-01535-3.","journal-title":"Cardiovasc Diabetol"},{"key":"1431_CR34","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/s12933-022-01616-3","volume":"21","author":"J Sabbatinelli","year":"2022","unstructured":"Sabbatinelli J, Giuliani A, Bonfigli AR, Ramini D, Matacchione G, Campolucci C, Ceka A, Tortato E, Rippo MR, Procopio AD, Moretti M, Olivieri F. Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study. Cardiovasc Diabetol. 2022;21:180.","journal-title":"Cardiovasc Diabetol"},{"key":"1431_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-024-02351-7","author":"J Sabbatinelli","year":"2024","unstructured":"Sabbatinelli J, Giuliani A, Kwiatkowska KM, Matacchione G, Belloni A, Ramini D, Prattichizzo F, Pellegrini V, Piacenza F, Tortato E, Bonfigli AR, Gentilini D, Procopio AD, Garagnani P, Olivieri F, Bronte G. DNA methylation-derived biological age and long-term mortality risk in subjects with type 2 diabetes. Cardiovasc Diabetol. 2024. https:\/\/doi.org\/10.1186\/s12933-024-02351-7.","journal-title":"Cardiovasc Diabetol"},{"key":"1431_CR36","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.3390\/nu12041098","volume":"12","author":"J Sabbatinelli","year":"2020","unstructured":"Sabbatinelli J, Orlando P, Galeazzi R, Silvestri S, Cirilli I, Marcheggiani F, Dludla PV, Giuliani A, Bonfigli AR, Mazzanti L, Olivieri F, Antonicelli R, Tiano L. Ubiquinol ameliorates endothelial dysfunction in subjects with mild-to-moderate dyslipidemia: a randomized clinical trial. Nutrients. 2020;12:1098.","journal-title":"Nutrients"},{"key":"1431_CR37","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13049-016-0239-y","volume":"24","author":"U Schott","year":"2016","unstructured":"Schott U, Solomon C, Fries D, Bentzer P. The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review. Scand J Trauma Resusc Emerg Med. 2016;24:48.","journal-title":"Scand J Trauma Resusc Emerg Med"},{"key":"1431_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2022.106196","volume":"146","author":"F Shaik","year":"2022","unstructured":"Shaik F, Balderstone MJM, Arokiasamy S, Whiteford JR. Roles of syndecan-4 in cardiac injury and repair. Int J Biochem Cell Biol. 2022;146: 106196.","journal-title":"Int J Biochem Cell Biol"},{"key":"1431_CR39","doi-asserted-by":"publisher","first-page":"H448","DOI":"10.1152\/ajpheart.00287.2018","volume":"315","author":"H Shakeri","year":"2018","unstructured":"Shakeri H, Lemmens K, Gevaert AB, De Meyer GRY, Segers VFM. Cellular senescence links aging and diabetes in cardiovascular disease. Am J Physiol Heart Circ Physiol. 2018;315:H448\u201362.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"1431_CR40","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.3390\/biomedicines11041066","volume":"11","author":"ME Strand","year":"2023","unstructured":"Strand ME, Vanhaverbeke M, Henkens M, Sikking MA, Rypdal KB, Braathen B, Almaas VM, Tonnessen T, Christensen G, Heymans S, Lunde IG. Inflammation and syndecan-4 shedding from cardiac cells in ischemic and non-ischemic heart disease. Biomedicines. 2023;11:1066.","journal-title":"Biomedicines"},{"key":"1431_CR41","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1111\/j.1464-5491.2011.03370.x","volume":"28","author":"R Testa","year":"2011","unstructured":"Testa R, Olivieri F, Sirolla C, Spazzafumo L, Rippo MR, Marra M, Bonfigli AR, Ceriello A, Antonicelli R, Franceschi C, Castellucci C, Testa I, Procopio AD. Leukocyte telomere length is associated with complications of type 2 diabetes mellitus. Diabet Med. 2011;28:1388\u201394.","journal-title":"Diabet Med"},{"key":"1431_CR42","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1369\/0022155415568995","volume":"63","author":"TT Vuong","year":"2015","unstructured":"Vuong TT, Reine TM, Sudworth A, Jenssen TG, Kolset SO. Syndecan-4 is a major syndecan in primary human endothelial cells in vitro, modulated by inflammatory stimuli and involved in wound healing. J Histochem Cytochem. 2015;63:280\u201392.","journal-title":"J Histochem Cytochem"},{"key":"1431_CR43","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1111\/j.1755-5922.2008.00051.x","volume":"26","author":"X Wang","year":"2008","unstructured":"Wang X, Keith JC Jr, Struthers AD, Feuerstein GZ. Assessment of arterial stiffness, a translational medicine biomarker system for evaluation of vascular risk. Cardiovasc Ther. 2008;26:214\u201323.","journal-title":"Cardiovasc Ther"},{"key":"1431_CR44","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1089\/gtmb.2014.0274","volume":"19","author":"XS Wang","year":"2015","unstructured":"Wang XS, Yang W, Luo T, Wang JM, Jing YY. Serum endocan levels are correlated with the presence and severity of coronary artery disease in patients with hypertension. Genet Test Mol Biomarkers. 2015;19:124\u20137.","journal-title":"Genet Test Mol Biomarkers"},{"key":"1431_CR45","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1093\/ckj\/sfz042","volume":"12","author":"O Yilmaz","year":"2019","unstructured":"Yilmaz O, Afsar B, Ortiz A, Kanbay M. The role of endothelial glycocalyx in health and disease. Clin Kidney J. 2019;12:611\u20139.","journal-title":"Clin Kidney J"},{"key":"1431_CR46","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13094","volume":"19","author":"MJ Yousefzadeh","year":"2020","unstructured":"Yousefzadeh MJ, Zhao J, Bukata C, Wade EA, McGowan SJ, Angelini LA, Bank MP, Gurkar AU, McGuckian CA, Calubag MF, Kato JI, Burd CE, Robbins PD, Niedernhofer LJ. Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice. Aging Cell. 2020;19: e13094.","journal-title":"Aging Cell"},{"key":"1431_CR47","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s42358-022-00254-3","volume":"62","author":"J Zhao","year":"2022","unstructured":"Zhao J, Ye X, Zhang Z. Syndecan-4 is correlated with disease activity and serological characteristic of rheumatoid arthritis. Adv Rheumatol. 2022;62:21.","journal-title":"Adv Rheumatol"}],"container-title":["Diabetology &amp; Metabolic Syndrome"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13098-024-01431-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13098-024-01431-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13098-024-01431-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T01:04:02Z","timestamp":1724115842000},"score":1,"resource":{"primary":{"URL":"https:\/\/dmsjournal.biomedcentral.com\/articles\/10.1186\/s13098-024-01431-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,20]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1431"],"URL":"https:\/\/doi.org\/10.1186\/s13098-024-01431-8","relation":{},"ISSN":["1758-5996"],"issn-type":[{"value":"1758-5996","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,20]]},"assertion":[{"value":"14 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study on subjects with type 2 diabetes was approved by the Institutional Review Board of IRCCS INRCA hospital (approval no. 34\/CdB\/03). The QHHC-FMD-PILOT study was conducted according to the guidelines of the Declaration of Helsinki and approved by the IRB of the INRCA in Ancona, Italy (Protocol Code: ACTRN12619000436178; 12\/2016).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"203"}}