Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2013

Open Access 01-12-2013 | Original investigation

Plasma concentrations of extracellular matrix protein fibulin-1 are related to cardiovascular risk markers in chronic kidney disease and diabetes

Authors: Alexandra Scholze, Else-Marie Bladbjerg, Johannes J Sidelmann, Axel CP Diederichsen, Hans Mickley, Mads Nybo, W Scott Argraves, Peter Marckmann, Lars M Rasmussen

Published in: Cardiovascular Diabetology | Issue 1/2013

Login to get access

Abstract

Background

Fibulin-1 is one of a few extracellular matrix proteins present in blood in high concentrations. We aimed to define the relationship between plasma fibulin-1 levels and risk markers of cardiovascular disease.

Methods

Plasma fibulin-1 was determined in subjects with chronic kidney disease (n = 32; median age 62.5, inter-quartile range 51 – 73 years) and 60 age-matched control subjects. Among kidney disease patients serological biomarkers related to cardiovascular disease (fibrinogen, interleukin 6, C-reactive protein) were measured. Arterial applanation tonometry was used to determine central hemodynamic and arterial stiffness indices.

Results

We observed a positive correlation of fibulin-1 levels with age (r = 0.38; p = 0.033), glycated hemoglobin (r = 0.80; p = 0.003), creatinine (r = 0.35; p = 0.045), and fibrinogen (r = 0.39; p = 0.027). Glomerular filtration rate and fibulin-1 were inversely correlated (r = −0.57; p = 0.022). There was a positive correlation between fibulin-1 and central pulse pressure (r = 0.44; p = 0.011) and central augmentation pressure (r = 0.55; p = 0.001). In a multivariable regression model, diabetes, creatinine, fibrinogen and central augmentation pressure were independent predictors of plasma fibulin-1.

Conclusion

Increased plasma fibulin-1 levels were associated with diabetes and impaired kidney function. Furthermore, fibulin-1 levels were associated with hemodynamic cardiovascular risk markers. Fibulin-1 is a candidate in the pathogenesis of cardiovascular disease observed in chronic kidney disease and diabetes.
Appendix
Available only for authorised users
Literature
1.
go back to reference Cangemi C, Skov V, Poulsen MK, Funder J, Twal WO, Gall MA, Hjortdal V, Jespersen ML, Kruse TA, Aagard J, Parving HH, Knudsen S, Høilund-Carlsen PF, Rossing P, Henriksen JE, Argraves WS, Rasmussen LM: Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes. Clin Chem. 2011, 57: 1556-1565. 10.1373/clinchem.2011.162966.CrossRefPubMed Cangemi C, Skov V, Poulsen MK, Funder J, Twal WO, Gall MA, Hjortdal V, Jespersen ML, Kruse TA, Aagard J, Parving HH, Knudsen S, Høilund-Carlsen PF, Rossing P, Henriksen JE, Argraves WS, Rasmussen LM: Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes. Clin Chem. 2011, 57: 1556-1565. 10.1373/clinchem.2011.162966.CrossRefPubMed
2.
go back to reference Argraves WS, Greene LM, Cooley MA, Gallagher WM: Fibulins: physiological and disease perspectives. EMBO Rep. 2003, 4: 1127-1131. 10.1038/sj.embor.7400033.PubMedCentralCrossRefPubMed Argraves WS, Greene LM, Cooley MA, Gallagher WM: Fibulins: physiological and disease perspectives. EMBO Rep. 2003, 4: 1127-1131. 10.1038/sj.embor.7400033.PubMedCentralCrossRefPubMed
3.
go back to reference Hungerford JE, Hoeffler JP, Bowers CW, Dahm LM, Falchetto R, Shabanowitz J, Hunt DF, Little CD: Identification of a novel marker for primordial smooth muscle and its differential expression pattern in contractile vs noncontractile cells. J Cell Biol. 1997, 137: 925-937. 10.1083/jcb.137.4.925.PubMedCentralCrossRefPubMed Hungerford JE, Hoeffler JP, Bowers CW, Dahm LM, Falchetto R, Shabanowitz J, Hunt DF, Little CD: Identification of a novel marker for primordial smooth muscle and its differential expression pattern in contractile vs noncontractile cells. J Cell Biol. 1997, 137: 925-937. 10.1083/jcb.137.4.925.PubMedCentralCrossRefPubMed
4.
go back to reference Roark EF, Keene DR, Haudenschild CC, Godyna S, Little CD, Argraves WS: The association of human fibulin-1 with elastic fibers: an immunohistological, ultrastructural, and RNA study. J Histochem Cytochem. 1995, 43: 401-411. 10.1177/43.4.7534784.CrossRefPubMed Roark EF, Keene DR, Haudenschild CC, Godyna S, Little CD, Argraves WS: The association of human fibulin-1 with elastic fibers: an immunohistological, ultrastructural, and RNA study. J Histochem Cytochem. 1995, 43: 401-411. 10.1177/43.4.7534784.CrossRefPubMed
5.
go back to reference Redfern CH, Degtyarev MY, Kwa AT, Salomonis N, Cotte N, Nanevicz T, Fidelman N, Desai K, Vranizan K, Lee EK, Coward P, Shah N, Warrington JA, Fishman GI, Bernstein D, Baker AJ, Conklin BR: Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy. PNAS. 2000, 97: 4826-4831. 10.1073/pnas.97.9.4826.PubMedCentralCrossRefPubMed Redfern CH, Degtyarev MY, Kwa AT, Salomonis N, Cotte N, Nanevicz T, Fidelman N, Desai K, Vranizan K, Lee EK, Coward P, Shah N, Warrington JA, Fishman GI, Bernstein D, Baker AJ, Conklin BR: Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy. PNAS. 2000, 97: 4826-4831. 10.1073/pnas.97.9.4826.PubMedCentralCrossRefPubMed
6.
go back to reference Kruger R, Schutte R, Huisman HW, Argraves WS, Rasmussen LM, Olsen MH, Schutte AE: NT-proBNP is associated with fibulin-1 in Africans: The SAfrEIC study. Atherosclerosis. 2012, 222: 216-221. 10.1016/j.atherosclerosis.2012.01.045.CrossRefPubMed Kruger R, Schutte R, Huisman HW, Argraves WS, Rasmussen LM, Olsen MH, Schutte AE: NT-proBNP is associated with fibulin-1 in Africans: The SAfrEIC study. Atherosclerosis. 2012, 222: 216-221. 10.1016/j.atherosclerosis.2012.01.045.CrossRefPubMed
7.
go back to reference Godyna S, Diaz-Ricart M, Argraves WS: Fibulin-1 mediates platelet adhesion via a bridge of fibrinogen. Blood. 1996, 88: 2569-2577.PubMed Godyna S, Diaz-Ricart M, Argraves WS: Fibulin-1 mediates platelet adhesion via a bridge of fibrinogen. Blood. 1996, 88: 2569-2577.PubMed
8.
go back to reference Holvoet P, Collen D: Thrombosis and atherosclerosis. Curr Opin Lipidol. 1997, 8: 320-328. 10.1097/00041433-199710000-00012.CrossRefPubMed Holvoet P, Collen D: Thrombosis and atherosclerosis. Curr Opin Lipidol. 1997, 8: 320-328. 10.1097/00041433-199710000-00012.CrossRefPubMed
9.
go back to reference Tran H, Tanaka A, Litvinovich SV, Medved LV, Haudenschild CC, Argraves WS: The interaction of fibulin-1 with fibrinogen. A potential role in hemostasis and thrombosis. J Biol Chem. 1995, 270: 19458-19464. 10.1074/jbc.270.33.19458.CrossRefPubMed Tran H, Tanaka A, Litvinovich SV, Medved LV, Haudenschild CC, Argraves WS: The interaction of fibulin-1 with fibrinogen. A potential role in hemostasis and thrombosis. J Biol Chem. 1995, 270: 19458-19464. 10.1074/jbc.270.33.19458.CrossRefPubMed
10.
go back to reference Argraves WS, Tanaka A, Smith EP, Twal WO, Argraves KM, Fan D, Haudenschild CC: Fibulin-1 and fibrinogen in human atherosclerotic lesions. Histochem Cell Biol. 2009, 132: 559-565. 10.1007/s00418-009-0628-7.CrossRefPubMed Argraves WS, Tanaka A, Smith EP, Twal WO, Argraves KM, Fan D, Haudenschild CC: Fibulin-1 and fibrinogen in human atherosclerotic lesions. Histochem Cell Biol. 2009, 132: 559-565. 10.1007/s00418-009-0628-7.CrossRefPubMed
11.
go back to reference Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 1999, 130: 461-470.CrossRefPubMed Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 1999, 130: 461-470.CrossRefPubMed
12.
go back to reference Diederichsen AC, Sand NP, Nørgaard B, Lambrechtsen J, Jensen JM, Munkholm H, Aziz A, Gerke O, Egstrup K, Larsen ML, Petersen H, Høilund-Carlsen PF, Mickley H: Discrepancy between coronary artery calcium score and HeartScore in middle-aged Danes: the DanRisk study. Eur J Prev Cardiol. 2012, 19: 558-564. 10.1177/1741826711409172.CrossRefPubMed Diederichsen AC, Sand NP, Nørgaard B, Lambrechtsen J, Jensen JM, Munkholm H, Aziz A, Gerke O, Egstrup K, Larsen ML, Petersen H, Høilund-Carlsen PF, Mickley H: Discrepancy between coronary artery calcium score and HeartScore in middle-aged Danes: the DanRisk study. Eur J Prev Cardiol. 2012, 19: 558-564. 10.1177/1741826711409172.CrossRefPubMed
13.
go back to reference Argraves WS, Dickerson K, Burgess WH, Ruoslahti E: Fibulin, a novel protein that interacts with the fibronectin receptor β subunit cytoplasmic domain. Cell. 1989, 58: 623-629. 10.1016/0092-8674(89)90097-4.CrossRefPubMed Argraves WS, Dickerson K, Burgess WH, Ruoslahti E: Fibulin, a novel protein that interacts with the fibronectin receptor β subunit cytoplasmic domain. Cell. 1989, 58: 623-629. 10.1016/0092-8674(89)90097-4.CrossRefPubMed
14.
go back to reference Pauca AL, O’Rourke MF, Kon ND: Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension. 2001, 38: 932-937. 10.1161/hy1001.096106.CrossRefPubMed Pauca AL, O’Rourke MF, Kon ND: Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension. 2001, 38: 932-937. 10.1161/hy1001.096106.CrossRefPubMed
15.
go back to reference Frimodt-Møller M, Nielsen AH, Kamper AL, Strandgaard S: Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease. Nephrol Dial Transplant. 2008, 23: 594-600.CrossRefPubMed Frimodt-Møller M, Nielsen AH, Kamper AL, Strandgaard S: Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease. Nephrol Dial Transplant. 2008, 23: 594-600.CrossRefPubMed
16.
go back to reference Chan MY, Lin M, Lucas J, Moseley A, Thompson JW, Cyr D, Ueda H, Kajikawa M, Ortel TL, Becker RC: Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor. Thromb Haemost. 2012, 108: 1180-1191. 10.1160/TH12-05-0310.CrossRefPubMed Chan MY, Lin M, Lucas J, Moseley A, Thompson JW, Cyr D, Ueda H, Kajikawa M, Ortel TL, Becker RC: Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor. Thromb Haemost. 2012, 108: 1180-1191. 10.1160/TH12-05-0310.CrossRefPubMed
17.
go back to reference Kaur P, Rizk NM, Ibrahim S, Younes N, Uppal A, Dennis K, Karve T, Blakeslee K, Kwagyan J, Zirie M, Ressom HW, Cheema AK: iTRAQ-based quantitative protein expression profiling and MRM verification of markers in type 2 diabetes. J Proteom Res. 2012, 11: 5527-5539. 10.1021/pr300798z.CrossRef Kaur P, Rizk NM, Ibrahim S, Younes N, Uppal A, Dennis K, Karve T, Blakeslee K, Kwagyan J, Zirie M, Ressom HW, Cheema AK: iTRAQ-based quantitative protein expression profiling and MRM verification of markers in type 2 diabetes. J Proteom Res. 2012, 11: 5527-5539. 10.1021/pr300798z.CrossRef
18.
go back to reference Neiman M, Hedberg JJ, Dönnes PR, Schuppe-Koistinen I, Hanschke S, Schindler R, Uhlén M, Schwenk JM, Nilsson P: Plasma profiling reveals human fibulin-1 as candidate marker for renal impairment. J Proteom Res. 2011, 10: 4925-4934. 10.1021/pr200286c.CrossRef Neiman M, Hedberg JJ, Dönnes PR, Schuppe-Koistinen I, Hanschke S, Schindler R, Uhlén M, Schwenk JM, Nilsson P: Plasma profiling reveals human fibulin-1 as candidate marker for renal impairment. J Proteom Res. 2011, 10: 4925-4934. 10.1021/pr200286c.CrossRef
19.
go back to reference Sjøland JA, Sidelmann JJ, Braband M, Pedersen RS, Esbensen K, Standeven KF, Ariëns RA, Gram J: Fibrin clot structure in patients with end-stage renal disease. Thromb Haemost. 2007, 98: 339-345.PubMed Sjøland JA, Sidelmann JJ, Braband M, Pedersen RS, Esbensen K, Standeven KF, Ariëns RA, Gram J: Fibrin clot structure in patients with end-stage renal disease. Thromb Haemost. 2007, 98: 339-345.PubMed
20.
go back to reference Koyama H, Nishizawa Y: AGEs/RAGE in CKD: irreversible metabolic memory road toward CVD?. Eur J Clin Invest. 2010, 40: 623-635. 10.1111/j.1365-2362.2010.02298.x.CrossRefPubMed Koyama H, Nishizawa Y: AGEs/RAGE in CKD: irreversible metabolic memory road toward CVD?. Eur J Clin Invest. 2010, 40: 623-635. 10.1111/j.1365-2362.2010.02298.x.CrossRefPubMed
21.
go back to reference Thornalley PJ, Rabbani N: Protein damage in diabetes and uremia-identifying hotspots of proteome damage where minimal modification is amplified to marked pathophysiological effect. Free Radic Res. 2011, 45: 89-100. 10.3109/10715762.2010.534162.CrossRefPubMed Thornalley PJ, Rabbani N: Protein damage in diabetes and uremia-identifying hotspots of proteome damage where minimal modification is amplified to marked pathophysiological effect. Free Radic Res. 2011, 45: 89-100. 10.3109/10715762.2010.534162.CrossRefPubMed
22.
go back to reference O’Rourke MF, Hashimoto J: Arterial stiffness – A modifiable cardiovascular risk factor?. J Cardiopulm Rehabil Prev. 2008, 28: 225-237.CrossRefPubMed O’Rourke MF, Hashimoto J: Arterial stiffness – A modifiable cardiovascular risk factor?. J Cardiopulm Rehabil Prev. 2008, 28: 225-237.CrossRefPubMed
23.
go back to reference Denardo SJ, Nandyala R, Freeman GL, Pierce GL, Nichols WW: Pulse wave analysis of the aortic pressure waveform in severe left ventricular systolic dysfunction. Circ Heart Fail. 2010, 3: 149-156. 10.1161/CIRCHEARTFAILURE.109.862383.CrossRefPubMed Denardo SJ, Nandyala R, Freeman GL, Pierce GL, Nichols WW: Pulse wave analysis of the aortic pressure waveform in severe left ventricular systolic dysfunction. Circ Heart Fail. 2010, 3: 149-156. 10.1161/CIRCHEARTFAILURE.109.862383.CrossRefPubMed
24.
go back to reference Reinhard H, Nybo M, Hansen PR, Wiinberg N, Kjær A, Petersen CL, Winther K, Parving HH, Rasmussen LM, Rossing P, Jacobsen PK: Osteoprotegerin and coronary artery disease in type 2 diabetic patients with microalbuminuria. Cardiovasc Diabetol. 2011, 10: 70-10.1186/1475-2840-10-70.PubMedCentralCrossRefPubMed Reinhard H, Nybo M, Hansen PR, Wiinberg N, Kjær A, Petersen CL, Winther K, Parving HH, Rasmussen LM, Rossing P, Jacobsen PK: Osteoprotegerin and coronary artery disease in type 2 diabetic patients with microalbuminuria. Cardiovasc Diabetol. 2011, 10: 70-10.1186/1475-2840-10-70.PubMedCentralCrossRefPubMed
25.
go back to reference Poulsen MK, Nybo M, Dahl J, Hosbond S, Poulsen TS, Johansen A, Høilund-Carlsen PF, Beck-Nielsen H, Rasmussen LM, Henriksen JE: Plasma osteoprotegrin is related to carotid and peripheral arterial disease, but not to myocardial ischemia in type 2 diabetes mellitus. Cardiovasc Diabetol. 2011, 10: 76-10.1186/1475-2840-10-76.PubMedCentralCrossRefPubMed Poulsen MK, Nybo M, Dahl J, Hosbond S, Poulsen TS, Johansen A, Høilund-Carlsen PF, Beck-Nielsen H, Rasmussen LM, Henriksen JE: Plasma osteoprotegrin is related to carotid and peripheral arterial disease, but not to myocardial ischemia in type 2 diabetes mellitus. Cardiovasc Diabetol. 2011, 10: 76-10.1186/1475-2840-10-76.PubMedCentralCrossRefPubMed
26.
go back to reference Reinhard H, Lajer M, Gall MA, Tarnow L, Parving HH, Rasmussen LM, Rossing P: Osteoprotegerin and mortality in type 2 Diabetic patients. Diabetes Care. 2010, 33: 2561-2566. 10.2337/dc10-0858.PubMedCentralCrossRefPubMed Reinhard H, Lajer M, Gall MA, Tarnow L, Parving HH, Rasmussen LM, Rossing P: Osteoprotegerin and mortality in type 2 Diabetic patients. Diabetes Care. 2010, 33: 2561-2566. 10.2337/dc10-0858.PubMedCentralCrossRefPubMed
27.
go back to reference Venuraju SM, Yerramasu A, Corder R, Lahiri A: Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. J Am Coll Cardiol. 2010, 55: 2049-2061. 10.1016/j.jacc.2010.03.013.CrossRefPubMed Venuraju SM, Yerramasu A, Corder R, Lahiri A: Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. J Am Coll Cardiol. 2010, 55: 2049-2061. 10.1016/j.jacc.2010.03.013.CrossRefPubMed
28.
go back to reference Garcia A, Eiras S, Parguina AF, Alonso J, Rosa I, Salgado-Somoza A, Rico TY, Teijeira-Fernandez E, Gonzales-Juanatey JR: High-resolution two-dimensional gel electrophoresis analysis of atrial tissue proteome reveals down-regulation of fibulin-1 in atrial fibrillation. Int J Cardiol. 2011, 150: 283-290. 10.1016/j.ijcard.2010.04.036.CrossRefPubMed Garcia A, Eiras S, Parguina AF, Alonso J, Rosa I, Salgado-Somoza A, Rico TY, Teijeira-Fernandez E, Gonzales-Juanatey JR: High-resolution two-dimensional gel electrophoresis analysis of atrial tissue proteome reveals down-regulation of fibulin-1 in atrial fibrillation. Int J Cardiol. 2011, 150: 283-290. 10.1016/j.ijcard.2010.04.036.CrossRefPubMed
Metadata
Title
Plasma concentrations of extracellular matrix protein fibulin-1 are related to cardiovascular risk markers in chronic kidney disease and diabetes
Authors
Alexandra Scholze
Else-Marie Bladbjerg
Johannes J Sidelmann
Axel CP Diederichsen
Hans Mickley
Mads Nybo
W Scott Argraves
Peter Marckmann
Lars M Rasmussen
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2013
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-12-6

Other articles of this Issue 1/2013

Cardiovascular Diabetology 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine