Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes
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Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes. / Cangemi, Claudia; Skov, Vibe; Poulsen, Michael Kjaer; Funder, Jonas; Twal, Waleed O; Gall, Mari-Anne; Hjortdal, Vibeke; Jespersen, Marie Louise; Kruse, Torben A; Aagard, Jan; Parving, Hans-Henrik; Knudsen, Steen; Høilund-Carlsen, Poul-Flemming; Rossing, Peter; Henriksen, Jan Erik; Argraves, William Scott; Rasmussen, Lars Melholt.
I: Clinical Chemistry, Bind 57, Nr. 11, 11.2011, s. 1556-65.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes
AU - Cangemi, Claudia
AU - Skov, Vibe
AU - Poulsen, Michael Kjaer
AU - Funder, Jonas
AU - Twal, Waleed O
AU - Gall, Mari-Anne
AU - Hjortdal, Vibeke
AU - Jespersen, Marie Louise
AU - Kruse, Torben A
AU - Aagard, Jan
AU - Parving, Hans-Henrik
AU - Knudsen, Steen
AU - Høilund-Carlsen, Poul-Flemming
AU - Rossing, Peter
AU - Henriksen, Jan Erik
AU - Argraves, William Scott
AU - Rasmussen, Lars Melholt
PY - 2011/11
Y1 - 2011/11
N2 - BACKGROUND: Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined.METHODS: Mammary artery specimens from 17 men with type 2 diabetes and 18 nondiabetic individuals were used for microarray expression profiling, quantitative real-time PCR, immunoassay, and immunohistochemical analyses. A derived candidate marker, fibulin-1, which is an elastin-associated matrix molecule, was measured immunochemically in plasma from (a) 70 patients scheduled for vascular surgery, (b) 305 patients with type 2 diabetes examined with carotid ultrasonography and echocardiography, and (c) 308 patients with type 2 diabetes, followed for 15 years.RESULTS: The most upregulated transcript in nonatherosclerotic arterial tissue from patients with type 2 diabetes encoded the extracellular matrix protein, fibulin-1. Higher concentrations of fibulin-1-protein were present in artery extracts from patients with diabetes than extracts from individuals without diabetes, and increased fibulin-1 immunostaining was apparent around the external elastic lamina of diabetic arteries. Patients with diabetes displayed increased plasma concentrations of fibulin-1 (P = 0.006). Plasma fibulin-1 concentrations correlated with hemoglobin A(1c) (P < 0.001), arterial stiffness indices including pulse pressure (P < 0.001), and carotid compliance (P = 0.004), as well as plasma N-terminal pro-B-type natriuretic peptide concentrations (P < 0.001) and were predictive of 15-year mortality (P = 0.013).CONCLUSIONS: Fibulin-1 accumulates in the arterial wall and in plasma of patients with type 2 diabetes, and appears to be a factor associated with arterial extracellular matrix changes in type 2 diabetes.
AB - BACKGROUND: Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined.METHODS: Mammary artery specimens from 17 men with type 2 diabetes and 18 nondiabetic individuals were used for microarray expression profiling, quantitative real-time PCR, immunoassay, and immunohistochemical analyses. A derived candidate marker, fibulin-1, which is an elastin-associated matrix molecule, was measured immunochemically in plasma from (a) 70 patients scheduled for vascular surgery, (b) 305 patients with type 2 diabetes examined with carotid ultrasonography and echocardiography, and (c) 308 patients with type 2 diabetes, followed for 15 years.RESULTS: The most upregulated transcript in nonatherosclerotic arterial tissue from patients with type 2 diabetes encoded the extracellular matrix protein, fibulin-1. Higher concentrations of fibulin-1-protein were present in artery extracts from patients with diabetes than extracts from individuals without diabetes, and increased fibulin-1 immunostaining was apparent around the external elastic lamina of diabetic arteries. Patients with diabetes displayed increased plasma concentrations of fibulin-1 (P = 0.006). Plasma fibulin-1 concentrations correlated with hemoglobin A(1c) (P < 0.001), arterial stiffness indices including pulse pressure (P < 0.001), and carotid compliance (P = 0.004), as well as plasma N-terminal pro-B-type natriuretic peptide concentrations (P < 0.001) and were predictive of 15-year mortality (P = 0.013).CONCLUSIONS: Fibulin-1 accumulates in the arterial wall and in plasma of patients with type 2 diabetes, and appears to be a factor associated with arterial extracellular matrix changes in type 2 diabetes.
KW - Aged
KW - Biomarkers/metabolism
KW - Calcium-Binding Proteins/blood
KW - Cardiovascular Diseases/diagnosis
KW - Carotid Intima-Media Thickness
KW - Case-Control Studies
KW - Diabetes Mellitus, Type 2/complications
KW - Extracellular Matrix/metabolism
KW - Extracellular Matrix Proteins/metabolism
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Immunoassay
KW - Immunohistochemistry
KW - Male
KW - Mammary Arteries/metabolism
KW - Middle Aged
KW - Oligonucleotide Array Sequence Analysis
KW - Predictive Value of Tests
KW - Prospective Studies
KW - Real-Time Polymerase Chain Reaction
U2 - 10.1373/clinchem.2011.162966
DO - 10.1373/clinchem.2011.162966
M3 - Journal article
C2 - 21926180
VL - 57
SP - 1556
EP - 1565
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 11
ER -
ID: 247872524