Subscribe to RSS
DOI: 10.1160/TH08-02-0078
Elevated plasma fibronectin levels associated with venous thromboembolism
Financial support: This work was supported by grants from the National Institutes of Health (HL-21544), NIH-GCRC M0100833 and the Skaggs Scholar Program of The Scripps Research Institute.Publication History
Received
08 February 2008
Accepted after major revision
16 June 2008
Publication Date:
22 November 2017 (online)
Summary
Elevated plasma fibronectin levels occur in various clinical states including arterial disease. Increasing evidence suggests that atherothrombosis and venous thromboembolism (VTE) share common risk factors. To assess the hypothesis that high plasma fibronectin levels are associated with VTE, we compared plasma fibronectin levels in the Scripps Venous Thrombosis Registry for 113VTE cases vs. age and sex matched controls. VTE cases had significantly higher mean fibronectin concentration compared to controls (127% vs. 103%, p<0.0001); the difference was greater for idiopathic VTE cases compared to secondary VTE cases (133% vs. 120%, respectively). Using a cut-off of >90% of the control values, the odds ratio (OR) for association of VTE for fibronectin plasma levels above the 90th percentile were 9.37 (95% CI 2.73–32.2; p<0.001) and this OR remained significant after adjustment for sex, age, body mass index (BMI), factor V Leiden and prothrombin nt20210A (OR 7.60,95% CI 2.14–27.0; p=0.002). In particular, the OR was statistically significant for idiopathic VTE before and after these statistical adjustments. For the total male cohort, the OR was significant before and after statistical adjustments and was not significant for the total female cohort. In summary, our results suggest that elevated plasma fibronectin levels are associated with VTE especially in males, and extend the potential association between biomarkers and risk factors for arterial atherothrombosis and VTE.
-
References
- 1 Mosher DF. Fibronectin. San Diego, CA: Academic Press; 1989
- 2 Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci 2002; 115: 3861-3863.
- 3 Falcone DJ, Mated N, Shio H. et al. Lipoprotein-heparin-fibronectin-denatured collagen complexes enhance cholesteryl ester accumulation in macrophages. J Cell Biol 1984; 99: 1266-1274.
- 4 Ekmekci H, Ekmekci OB, Sonmez H. et al. Evaluation of fibronectin, vitronectin, and leptin levels in coronary artery disease: Impacts on thrombosis and thrombolysis. Clin Appl Thromb Hemost 2005; 11: 63-70.
- 5 Orem C, Durmus I, Kilinc D. et al. Plasma fibronectin level and its association with coronary artery disease and carotid intima-media thickness. Coron Artery Dis 2003; 14: 219-224.
- 6 Song KS, Kim HK, Shim W. et al. Plasma fibronectin levels in ischemic heart disease. Atherosclerosis 2001; 154: 449-453.
- 7 Mosher DF. Cross-linking of cold-insoluble globulin by fibrin-stabilizing factor. J Biol Chem 1975; 250: 6614-6621.
- 8 Mosher DF. Action of fibrin-stabilizing factor on cold-insoluble globulin and alpha2-macroglobulin in clotting plasma. J Biol Chem 1976; 251: 1639-1645.
- 9 Cho J, Mosher DF. Role of fibronectin assembly in platelet thrombus formation. J Thromb Haemost 2006; 04: 2533-2541.
- 10 Prandoni P, Bilora F, Marchiori A. et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003; 348: 1435-1441.
- 11 Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet 2005; 365: 1163-1174.
- 12 Deguchi H, Pecheniuk NM, Elias DJ. et al. Highdensity lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men. Circulation 2005; 112: 893-899.
- 13 Eichinger S, Pecheniuk NM, Hron G. et al. Highdensity lipoprotein and the risk of recurrent venous thromboembolism. Circulation 2007; 115: 1609-1614.
- 14 Vavalle JP, Wu SS, Hughey R. et al. Plasma fibronectin levels and coronary artery disease. J Thromb Haemost 2007; 05: 864-866.
- 15 Prandoni P. Venous thromboembolism and atherosclerosis: is there a link?. J Thromb Haemost 2007; 05 (Suppl. 01) 270-275.
- 16 Stathakis N, Fountas A, Tsianos E. Plasma fibronectin in normal subjects and in various disease states. J Clin Pathol 1981; 34: 504-508.
- 17 Plow EF, McEver RP, Coller BS. etal Related binding mechanisms for fibrinogen, fibronectin, von Willebrand factor, and thrombospondin on thrombin-stimulated human platelets. Blood 1985; 66: 724-727.
- 18 Gardner JM, Hynes RO. Interaction of fibronectin with its receptor on platelets. Cell 1985; 42: 439-448.
- 19 Hynes RO. Integrins: a family of cell surface receptors. Cell 1987; 48: 549-554.
- 20 Matuskova J, Chauhan AK, Cambien B. et al. Decreased plasma fibronectin leads to delayed thrombus growth in injured arterioles. Arterioscler Thromb Vascular Biol 2006; 26: 1391-1396.
- 21 Sakai T, Johnson KJ, Murozono M. et al. Plasma fibronectin support neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. Nat Med 2001; 07: 324-330.
- 22 Ni H, Yuen PST, Papalia JM. et al. Plasma fibronectin promotes thrombus growth and stability in injured arterioles. Proc Nat Acad Sci USA 2003; 100: 2415-2419.
- 23 Bastida E, Escolar G, Ordinas A. et al. Fibronectin is required for platelet adhesion and for thrombus formation on subendothelium and collagen surfaces. Blood 1987; 70: 1437-1442.
- 24 Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins. J Clin Path 1974; 27: 517-528.
- 25 Lopez JA, Kearon C, Lee AY. Deep venous thrombosis. Hematology Am Soc Hematol Educ Program 2004; 439-456.
- 26 Chauhan AK, Kisucka J, Cozzi M. et al. Prothrombotic effects of fibronectin isoforms containing the EDA domain. Arterioscler Thromb Vasc Biol 2008; 28: 296-301.