{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:45:39Z","timestamp":1790790339057,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AG063197"],"award-info":[{"award-number":["R21AG063197"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG27084-04S1"],"award-info":[{"award-number":["R01AG27084-04S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30DK56336"],"award-info":[{"award-number":["P30DK56336"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P60DK079626"],"award-info":[{"award-number":["P60DK079626"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1RR025777"],"award-info":[{"award-number":["UL1RR025777"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Syndecans (SDCs) are transmembrane proteins that are present on most cell types where they play a role in multiple physiological processes, including cell\u2013matrix adhesion and inflammation. Growing evidence suggests that elevated levels of both shed SDC1 and SDC4 are associated with hypertension and cardiovascular diseases, but their relationships with cardiovascular risk factors in healthy individuals are unknown. The primary objective of this study was to investigate whether serum levels of SDC4 and SDC1 were associated with body composition, hemodynamic parameters, pro-inflammatory cytokine concentrations, and urinary noradrenaline and dopamine levels in healthy women (17 African American and 20 European American) between the ages of 20 and 40 years old. Univariate analyses revealed only a significant (p &lt; 0.05) inverse correlation between serum SDC1 and body fat percentage. On the other hand, serum SDC4 was positively correlated with systolic blood pressure, diastolic blood pressure, and urinary levels of noradrenaline and dopamine. Serum SDC4 was also a significant predictor of systolic blood pressure in a multivariate regression model that included fat-free mass and urinary dopamine levels as significant independent variables. The result did not change even adjusting for race. Our findings indicate that SDC4 has an important role in the physiological regulation of blood pressure.<\/jats:p>","DOI":"10.3390\/biom11030342","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T20:53:21Z","timestamp":1614200001000},"page":"342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Circulating Levels of the Heparan Sulfate Proteoglycan Syndecan-4 Positively Associate with Blood Pressure in Healthy Premenopausal Women"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6345-7508","authenticated-orcid":false,"given":"Maria","family":"De Luca","sequence":"first","affiliation":[{"name":"Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Bryan","sequence":"additional","affiliation":[{"name":"Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary R.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a004952","DOI":"10.1101\/cshperspect.a004952","article-title":"Heparan Sulfate Proteoglycans","volume":"3","author":"Sarrazin","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chakravarti, R., and Adams, J.C. (2006). Comparative genomics of the syndecans defines an ancestral genomic context associated with matrilins in vertebrates. BMC Genom., 7.","DOI":"10.1186\/1471-2164-7-83"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1111\/febs.12174","article-title":"Mapping of matrix metalloproteinase cleavage sites on syndecan-1 and syndecan-4 ectodomains","volume":"280","author":"Multhaupt","year":"2013","journal-title":"FEBS J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1083\/jcb.148.4.811","article-title":"Shedding of Syndecan-1 and -4 Ectodomains Is Regulated by Multiple Signaling Pathways and Mediated by a Timp-3\u2013Sensitive Metalloproteinase","volume":"148","author":"Fitzgerald","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1111\/j.1742-4658.2010.07798.x","article-title":"Proteoglycans in health and disease: The multiple roles of syndecan shedding","volume":"277","author":"Itoh","year":"2010","journal-title":"FEBS J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrm2289","article-title":"Synergistic control of cell adhesion by integrins and syndecans","volume":"8","author":"Morgan","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00441-009-0829-3","article-title":"Syndecans as receptors and organizers of the extracellular matrix","volume":"339","author":"Xian","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35435","DOI":"10.1074\/jbc.M804172200","article-title":"Syndecan-1 Ectodomain Shedding Is Regulated by the Small GTPase Rab5","volume":"283","author":"Hayashida","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/ckj\/sfz042","article-title":"The role of endothelial glycocalyx in health and disease","volume":"12","author":"Yilmaz","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3389\/fcell.2020.00253","article-title":"The Emerging Role of the Mammalian Glycocalyx in Functional Membrane Organization and Immune System Regulation","volume":"8","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17308","DOI":"10.1073\/pnas.1413725111","article-title":"Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling","volume":"111","author":"Baeyens","year":"2014","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9547","DOI":"10.1074\/jbc.M113.541573","article-title":"Loss of Syndecan-1 Induces a Pro-inflammatory Phenotype in Endothelial Cells with a Dysregulated Response to Atheroprotective Flow","volume":"289","author":"Voyvodic","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.1161\/01.RES.0000101744.47866.D5","article-title":"Heparan Sulfate Proteoglycan Is a Mechanosensor on Endothelial Cells","volume":"93","author":"Florian","year":"2003","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1161\/CIRCULATIONAHA.106.684852","article-title":"Shedding of the Endothelial Glycocalyx in Patients Undergoing Major Vascular Surgery with Global and Regional Ischemia","volume":"116","author":"Rehm","year":"2007","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.2217\/bmm-2016-0163","article-title":"Endothelial glycocalyx layer shedding following lung resection","volume":"10","author":"Arthur","year":"2016","journal-title":"Biomarkers Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1100\/tsw.2010.88","article-title":"Sepsis-Induced Degradation of Endothelial Glycocalix","volume":"10","author":"Henrich","year":"2010","journal-title":"Sci. World J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11897-017-0320-5","article-title":"Endothelial Glycocalyx as Biomarker for Cardiovascular Diseases: Mechanistic and Clinical Implications","volume":"14","author":"Kim","year":"2017","journal-title":"Curr. Hear. Fail. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.atherosclerosis.2018.08.005","article-title":"Gender differences in the association of syndecan-4 with myocardial infarction: The population-based Troms\u00f8 Study","volume":"278","author":"Solbu","year":"2018","journal-title":"Atheroscler."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lipphardt, M., Dihazi, H., Maas, J.-H., Sch\u00e4fer, A.-K., Amlaz, S.I., Ratliff, B.B., Koziolek, M.J., and Wallbach, M. (2020). Syndecan-4 as a Marker of Endothelial Dysfunction in Patients with Resistant Hypertension. J. Clin. Med., 9.","DOI":"10.3390\/jcm9093051"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1253\/circj.CJ-15-0552","article-title":"Could Circulatory Syndecan-1 Be a Predictable Biomarker for Acute Kidney Injury in Patients with Acute Decompensated Heart Failure?","volume":"79","author":"Sueta","year":"2015","journal-title":"Circ. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/bph.14397","article-title":"Soluble syndecans: Biomarkers for diseases and therapeutic options","volume":"176","author":"Bertrand","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1161\/hq0102.100314","article-title":"Mechanical stress regulates syndecan-4 expression and redistribution in vascular smooth muscle cells","volume":"22","author":"Li","year":"2002","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"C517","DOI":"10.1152\/ajpcell.00093.2006","article-title":"Mechanical strain regulates syndecan-4 expression and shedding in smooth muscle cells through differential activation of MAP kinase signaling pathways","volume":"292","author":"Julien","year":"2007","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5703","DOI":"10.1021\/bi052263h","article-title":"Insulin Promotes Shedding of Syndecan Ectodomains from 3T3-L1 Adipocytes: A Proposed Mechanism for Stabilization of Extracellular Lipoprotein Lipase\u2020","volume":"45","author":"Reizes","year":"2006","journal-title":"Biochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1093\/eurheartj\/ehr048","article-title":"Red alert for women\u2019s heart: The urgent need for more research and knowledge on cardiovascular disease in women: Proceedings of the Workshop held in Brussels on Gender Differences in Cardiovascular disease, 29 September 2010","volume":"32","author":"Maas","year":"2011","journal-title":"Eur. Hear. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/MAJ.0000000000000308","article-title":"Racial Differences in Hypertension: Implications for High Blood Pressure Management","volume":"348","author":"Lackland","year":"2014","journal-title":"Am. J. Med Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/jhh.2008.36","article-title":"Effect of 4 weeks of aerobic or resistance exercise training on arterial stiffness, blood flow and blood pressure in pre- and stage-1 hypertensives","volume":"22","author":"Collier","year":"2008","journal-title":"J. Hum. Hypertens."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1139\/apnm-2015-0512","article-title":"Systolic blood pressure response after high-intensity interval exercise is independently related to decreased small arterial elasticity in normotensive African American women","volume":"41","author":"Carter","year":"2016","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1161\/01.HYP.26.3.503","article-title":"Noninvasive Pulse Wave Analysis for the Early Detection of Vascular Disease","volume":"26","author":"Cohn","year":"1995","journal-title":"Hypertension"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1161\/HYPERTENSIONAHA.110.157727","article-title":"Dopamine Receptors","volume":"57","author":"Zeng","year":"2011","journal-title":"Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.ijcard.2018.09.035","article-title":"Changes in fat mass and fat-free-mass are associated with incident hypertension in four population-based studies from Germany","volume":"274","author":"Ittermann","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.neuroimage.2012.09.005","article-title":"Fat-free body mass but not fat mass is associated with reduced gray matter volume of cortical brain regions implicated in autonomic and homeostatic regulation","volume":"64","author":"Weise","year":"2013","journal-title":"NeuroImage"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40885-018-0102-8","article-title":"Arterial stiffness and hypertension","volume":"24","author":"Oh","year":"2018","journal-title":"Clin. Hypertens."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1159\/000181816","article-title":"Catecholamines and Blood Pressure Regulation","volume":"34","author":"Mannelli","year":"1990","journal-title":"Horm. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Johansson, P.I., Bro-Jeppesen, J., Kjaergaard, J., Wanscher, M., Hassager, C., and Ostrowski, S.R. (2015). Sympathoadrenal Activation and Endothelial Damage Are Inter Correlated and Predict Increased Mortality in Patients Resuscitated after Out-Of-Hospital Cardiac Arrest. A Post Hoc Sub-Study of Patients from the TTM-Trial. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120914"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"R32","DOI":"10.1186\/cc12532","article-title":"Acute myocardial infarction is associated with endothelial glycocalyx and cell damage and a parallel increase in circulating catecholamines","volume":"17","author":"Ostrowski","year":"2013","journal-title":"Crit. Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-54937-x","article-title":"Syndecan-1 Predicts Outcome in Patients with ST-Segment Elevation Infarction Independent from Infarct-related Myocardial Injury","volume":"9","author":"Wernly","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"200161","DOI":"10.1098\/rsob.200161","article-title":"Endothelial cells, neutrophils and platelets: Getting to the bottom of an inflammatory triangle","volume":"10","author":"Dehghani","year":"2020","journal-title":"Open Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3233\/BIR-180205","article-title":"Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target","volume":"56","author":"Harding","year":"2019","journal-title":"Biorheol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1113\/JP273043","article-title":"Hypertension-induced remodelling: On the interactions of cardiac risk factors","volume":"595","author":"Tomek","year":"2017","journal-title":"J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e013518","DOI":"10.1161\/JAHA.119.013518","article-title":"Syndecan-4 Protects the Heart From the Profibrotic Effects of Thrombin-Cleaved Osteopontin","volume":"9","author":"Herum","year":"2020","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1378\/chest.06-2703","article-title":"Obstructive Sleep Apnea, Hypertension, and Their Interaction on Arterial Stiffness and Heart Remodeling","volume":"131","author":"Drager","year":"2007","journal-title":"Chest"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10719-019-09869-z","article-title":"Acute exercise increases syndecan-1 and -4 serum concentrations","volume":"36","author":"Lee","year":"2019","journal-title":"Glycoconj. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1001\/2013.jamainternmed.857","article-title":"Racial Differences in the Impact of Elevated Systolic Blood Pressure on Stroke Risk","volume":"173","author":"Howard","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1161\/CIRCULATIONAHA.106.643940","article-title":"Ethnic and Gender Differences in Ambulatory Blood Pressure Trajectories","volume":"114","author":"Wang","year":"2006","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1161\/01.CIR.54.2.319","article-title":"Studies of blood pressures in children, ages 5-14 years, in a total biracial community: The Bogalusa Heart Study","volume":"54","author":"Voors","year":"1976","journal-title":"Circulation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1210\/jc.2003-031446","article-title":"Sodium Retention in Black and White Female Adolescents in Response to Salt Intake","volume":"89","author":"Palacios","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7","DOI":"10.5049\/EBP.2015.13.1.7","article-title":"Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction","volume":"13","author":"Choi","year":"2015","journal-title":"Electrolytes Blood Press."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1681\/ASN.2014050430","article-title":"Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity","volume":"26","author":"Engberink","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"De Luca, M., Vecchie\u2019, D., Athmanathan, B., Gopalkrishna, S., Valcin, J.A., Swain, T.M., Sertie, R., Wekesa, K., Rowe, G.C., and Bailey, S.M. (2019). Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet (Running Title: Sdc4 Deficiency Affects Metabolic Phenotypes). Nutr., 11.","DOI":"10.3390\/nu11112810"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kasza, I., Suh, Y., Wollny, D., Clark, R.J., Roopra, A., Colman, R.J., MacDougald, O.A., Shedd, T.A., Nelson, D.W., and Yen, M.-I. (2014). Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004514"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3389\/fimmu.2020.00769","article-title":"Proteoglycans in Obesity-Associated Metabolic Dysfunction and Meta-Inflammation","volume":"11","author":"Pessentheiner","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jacc.2005.01.072","article-title":"Insights From the NHLBI-Sponsored Women\u2019s Ischemia Syndrome Evaluation (WISE) Study","volume":"47","author":"Shaw","year":"2006","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/3\/342\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:28:02Z","timestamp":1760160482000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/3\/342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["biom11030342"],"URL":"https:\/\/doi.org\/10.3390\/biom11030342","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]}}}