{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:50:32Z","timestamp":1771469432466,"version":"3.50.1"},"reference-count":28,"publisher":"American Diabetes Association","issue":"2","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,2,1]]},"abstract":"<jats:p>OBJECTIVE\u2014 Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Elevated plasma levels of cellular fibronectin therefore reflect loss of endothelial cell polarization or injury to blood vessels. Consequently, elevated plasma levels of circulating cellular fibronectin have been described in clinical syndromes with vascular damage, although not in diabetes or atherosclerosis.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014 We determined fibronectin levels in 52 patients with type 1 diabetes, 50 patients with type 2 diabetes, 54 patients with a history of ischemic stroke, 23 patients with renal artery stenosis, and 64 healthy subjects.<\/jats:p>\n               <jats:p>RESULTS\u2014 Circulating cellular fibronectin was significantly elevated in patients with diabetes (4.3 \u00b1 2.8 \u03bcg\/ml) compared with patients with ischemic stroke (2.0 \u00b1 0.9 \u03bcg\/ml), patients with renovascular hypertension (1.7 \u00b1 1.1 \u03bcg\/ml), and healthy subjects(1.4 \u00b1 0.6 \u03bcg\/ml). Patients with diabetes and at least one cardiovascular risk factor had an almost 2.5-fold increase in cellular fibronectin compared with diabetic subjects without such a risk factor. In multivariate regression analysis, higher triglycerides, current or past cigarette smoking, and higher urinary albumin excretion were independently associated with an increase in circulating cellular fibronectin in diabetes.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014 These results suggest that circulating cellular fibronectin may be a marker protein for endothelial cell activation,especially in diabetes. Prospective studies are needed to explore this possibility.<\/jats:p>","DOI":"10.2337\/diacare.24.2.323","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T22:51:27Z","timestamp":1173135087000},"page":"323-327","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":78,"title":["Plasma Levels of Cellular Fibronectin in Diabetes"],"prefix":"10.2337","volume":"24","author":[{"given":"Suzan D.J.M.","family":"Kanters","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine (S.D.J.M.K.,J.-D.B.), the Julius Center for Patient-Oriented Research (A.A.), the Department of Neurology(A.A., R.C.J.M.F.), the Department of Nephrology and Hypertension (J.J.B.),and the Department of Hematology (R.F.), University Medical Center, Utrecht,the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Dirk","family":"Banga","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (S.D.J.M.K.,J.-D.B.), the Julius Center for Patient-Oriented Research (A.A.), the Department of Neurology(A.A., R.C.J.M.F.), the Department of Nephrology and Hypertension (J.J.B.),and the Department of Hematology (R.F.), University Medical Center, Utrecht,the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ale","family":"Algra","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (S.D.J.M.K.,J.-D.B.), the Julius Center for Patient-Oriented Research (A.A.), the Department of Neurology(A.A., R.C.J.M.F.), the Department of Nephrology and Hypertension (J.J.B.),and the Department of Hematology (R.F.), University Medical Center, Utrecht,the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rini C.J.M.","family":"Frijns","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (S.D.J.M.K.,J.-D.B.), the Julius Center for Patient-Oriented Research (A.A.), the Department of Neurology(A.A., R.C.J.M.F.), the Department of Nephrology and Hypertension (J.J.B.),and the Department of Hematology (R.F.), University Medical Center, Utrecht,the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaap J.","family":"Beutler","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (S.D.J.M.K.,J.-D.B.), the Julius Center for Patient-Oriented Research (A.A.), the Department of Neurology(A.A., R.C.J.M.F.), the Department of Nephrology and Hypertension (J.J.B.),and the Department of Hematology (R.F.), University Medical Center, Utrecht,the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"Fijnheer","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (S.D.J.M.K.,J.-D.B.), the Julius Center for Patient-Oriented Research (A.A.), the Department of Neurology(A.A., R.C.J.M.F.), the Department of Nephrology and Hypertension (J.J.B.),and the Department of Hematology (R.F.), University Medical Center, Utrecht,the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031216595975800_REF1","doi-asserted-by":"crossref","unstructured":"Hynes RO: Fibronectins. Sci Am\u2008254: 42-51,1986","DOI":"10.1038\/scientificamerican0686-42"},{"key":"2022031216595975800_REF2","doi-asserted-by":"crossref","unstructured":"Hynes RO: Molecular biology of fibronectin. Ann Rev Cell Biol\u20081: 67-90,1985","DOI":"10.1146\/annurev.cb.01.110185.000435"},{"key":"2022031216595975800_REF3","doi-asserted-by":"crossref","unstructured":"Yamada K, Kennedy DW: Fibroblast cellular and plasma fibronectin are similar but not identical. J Cell Biol\u200880: 492-498,1979","DOI":"10.1083\/jcb.80.2.492"},{"key":"2022031216595975800_REF4","doi-asserted-by":"crossref","unstructured":"Peters JH, Sporn LA, Ginsberg MH, Wagner DD: Human endothelial cells synthesize, process, and secrete fibronection molecules bearing an alternatively spliced type II homology (ED1). Blood\u200875: 1801-1808,1990","DOI":"10.1182\/blood.V75.9.1801.bloodjournal7591801"},{"key":"2022031216595975800_REF5","unstructured":"Peters JH, Maunder RJ, Woolf AD, Cochrane CG, Ginsberg MH: Elevated plasma levels of ED1+ (\u201ccellular\u201d) fibronectin in patients with vascular injury. J Lab Clin Med\u2008113: 586-597,1989"},{"key":"2022031216595975800_REF6","doi-asserted-by":"crossref","unstructured":"Friedman SA, de Groot C, Taylor R, Golditch B, Roberts JM: Plasma cellular fibronectin as a measure of endothelial involvement in preeclampsia and intrauterine growth retardation. Am J Obstet Gynecol\u2008170:838-841, 1994","DOI":"10.1016\/S0002-9378(94)70295-0"},{"key":"2022031216595975800_REF7","doi-asserted-by":"crossref","unstructured":"Van der Plas RM, Schiphorst ME, Huizinga EG, Hene RJ, Verdonck LF,Sixma JJ, Fijnheer R: Von Willebrand factor proteolysis is deficient in classis, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura. Blood\u200893: 3798-3802,1999","DOI":"10.1182\/blood.V93.11.3798.411k07_3798_3802"},{"key":"2022031216595975800_REF8","unstructured":"Voskuyl AE, Emeis JJ, Hazes JMW, Van Hogezand RA, Biemond I,Breedveld FC: Levels of circulating cellular fibronectin are increased in patients with rheumatoid vasculitis. Clin Exp Rheumatol\u200816:429-434, 1998"},{"key":"2022031216595975800_REF9","doi-asserted-by":"crossref","unstructured":"Fijnheer R, Frijns CJ, Korteweg J, Rommes H, Peters JH, Sixma JJ,Nieuwenhuis HK: The origin of P-selectin as a circulating plasma protein. Thromb Haemost\u200877:1081-1085, 1997","DOI":"10.1055\/s-0038-1656116"},{"key":"2022031216595975800_REF10","doi-asserted-by":"crossref","unstructured":"Andresen JL, Rasmussen L, Ledet T: Diabetic macroangiopathy and atherosclerosis. Diabetes\u200845(Suppl. 1): S91-S94, 1996","DOI":"10.2337\/diab.45.3.S91"},{"key":"2022031216595975800_REF11","doi-asserted-by":"crossref","unstructured":"Kanters SDJM, Algra A, De Bruin TWA, Erkelens DW, Banga JD:Intensive lipid lowering strategy in patients with diabetes mellitus. Diabet Med\u200816:500-508, 1999","DOI":"10.1046\/j.1464-5491.1999.00080.x"},{"key":"2022031216595975800_REF12","doi-asserted-by":"crossref","unstructured":"Ligtenberg PC, Blans M, Hoekstra JBL, Van der Tweel I, Erkelens DW:No effect of long-term physical activity on the glycemic control in type 1 diabetes patients: a cross-sectional study. Neth J Med\u200855: 59-64,1999","DOI":"10.1016\/S0300-2977(99)00039-X"},{"key":"2022031216595975800_REF13","doi-asserted-by":"crossref","unstructured":"Frijns CJM, Kappelle LJ, Van Gijn J, Nieuwenhuis HK, Sixma JJ,Fijnheer R: Soluble adhesion molecules reflect endothelial cell activation in ischemic stroke and in carotid atherosclerosis. Stroke\u200828: 2214-2218,1997","DOI":"10.1161\/01.STR.28.11.2214"},{"key":"2022031216595975800_REF14","doi-asserted-by":"crossref","unstructured":"Verhaar MC, Beutler JJ, Gaillard CA, Koomans HA, Fijnheer R,Rabelink TJ: Progressive vascular damage in hypertension is associated with increased levels of circulating P-selectin. J Hypertens\u200816:45-50, 1998","DOI":"10.1097\/00004872-199816010-00008"},{"key":"2022031216595975800_REF15","doi-asserted-by":"crossref","unstructured":"Garbasch C, Matthiessen ME, Olsen BE, Moe D, Kirkeby S:Immunohistochemistry of the intercellular matrix components and the epithelio-mesenchymal junction of the human tooth germ. Histochem J\u200826: 110-118,1994","DOI":"10.1007\/BF00157959"},{"key":"2022031216595975800_REF16","doi-asserted-by":"crossref","unstructured":"Cattoretti G, Pileri S, Parravicini C, Becker MH, Poggi S, Bifulco,C, Key G, D'Amato L, Sabattini E, Feudale E: Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections. J Pathol\u2008171:83-98, 1993","DOI":"10.1002\/path.1711710205"},{"key":"2022031216595975800_REF17","doi-asserted-by":"crossref","unstructured":"Liao Y-F, Wieder KG, Classen JM, Van De Water L: Identification of two amino acids within the EIIIA (ED-A) segment of fibronectin constituting the epitope for two function-blocking monoclonal antibodies. JBC\u2008274:17876-17884, 1999","DOI":"10.1074\/jbc.274.25.17876"},{"key":"2022031216595975800_REF18","doi-asserted-by":"crossref","unstructured":"Haffner SM: Management of dyslipidemia in adults with diabetes. Diabetes Care\u200821:160-178, 1998","DOI":"10.2337\/diacare.21.1.160"},{"key":"2022031216595975800_REF19","doi-asserted-by":"crossref","unstructured":"Dinneen SF, Gerstein HC: The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med\u2008157: 1413-1418,1997","DOI":"10.1001\/archinte.157.13.1413"},{"key":"2022031216595975800_REF20","doi-asserted-by":"crossref","unstructured":"Williams SB, Cusco JA, Roddy MA, Johnstone MT, Creager MA: Impaired nitric oxide\u2014mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J Am Coll Cardiol\u200827:567-574, 1996","DOI":"10.1016\/0735-1097(95)00522-6"},{"key":"2022031216595975800_REF21","doi-asserted-by":"crossref","unstructured":"Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA:Impaired endothelium-dependent vasodilation in patients with insulin-dependnet diabetes mellitus. Circulation\u200888: 2510-2516,1993","DOI":"10.1161\/01.CIR.88.6.2510"},{"key":"2022031216595975800_REF22","doi-asserted-by":"crossref","unstructured":"Vischer UM, Emeis JJ, Bilo HJG, Stehouwer CDA, Thomsen C, Rasmussen O, Hermansen K, Wollheim CB, Ingerslev J: von-Willebrand factor (vWf) as a plasma marker of endothelial activation in diabetes: improved reliability with parallel determination of the vWf propeptide (vWf:AgII). Thromb Haemost\u200880:1002-1007, 1998","DOI":"10.1055\/s-0037-1615401"},{"key":"2022031216595975800_REF23","doi-asserted-by":"crossref","unstructured":"Van Mourik JA, Boertjes R, Voorberg J, Huisveld IA, Fijnvandraat K,Van Genderen PJJ, Fijnheer R: Von Willebrand factor propeptide in vascular disorders: a tool for discriminating between acute and chronic endothelial cell perturbation. Blood\u200894:179-185, 1999","DOI":"10.1182\/blood.V94.1.179.413k18_179_185"},{"key":"2022031216595975800_REF24","doi-asserted-by":"crossref","unstructured":"Bauters C, Marotte F, Hamon M, Oliviero P, Farhadian F, Robert V,Samuel JL, Rappaport L: Accumulation of fetal fibronectin mRNAs after balloon denudation of rabbit arteries. Circulation\u200892: 904-911,1995","DOI":"10.1161\/01.CIR.92.4.904"},{"key":"2022031216595975800_REF25","doi-asserted-by":"crossref","unstructured":"Kornblihtt AR, Pesce CG, Alonso CR, Cramer P, Srebrow A, Werbajh S,Muro AF: The fibronectin gene as a model for splicing and transcription studies. FASEB J\u200810:248-257, 1996","DOI":"10.1096\/fasebj.10.2.8641558"},{"key":"2022031216595975800_REF26","doi-asserted-by":"crossref","unstructured":"Spirin KS, Saghizadeh M, Lewin SL, Zardi L, Kenney MC, Ljubimov AV:Basement membrane and growth factor gene expression in normal and diabetic human retinas. Curr Eye Res\u200818:490-499, 1999","DOI":"10.1076\/ceyr.18.6.490.5267"},{"key":"2022031216595975800_REF27","doi-asserted-by":"crossref","unstructured":"Peters DMP, Mosher DF: Localization of cell surface sites involved in fibronectin fibrillogenesis. J Cell Biol\u2008104: 121-130,1987","DOI":"10.1083\/jcb.104.1.121"},{"key":"2022031216595975800_REF28","doi-asserted-by":"crossref","unstructured":"Wang A, Cohen DS, Palmer E, Sheppard D: Polarized regulation of fibronectin secretion and alternative splicing by transforming growth factor\u03b2. J Biol Chem\u2008266:15598-15601, 1991","DOI":"10.1016\/S0021-9258(18)98447-4"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/24\/2\/323\/587137\/0240323.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/24\/2\/323\/587137\/0240323.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T17:38:23Z","timestamp":1647106703000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/24\/2\/323\/24208\/Plasma-Levels-of-Cellular-Fibronectin-in-Diabetes"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,2,1]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2001,2,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diacare.24.2.323","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,2,1]]}}}