Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Clinical Chemistry |
Volume | 57 |
Issue number | 11 |
Pages (from-to) | 1556-65 |
Number of pages | 10 |
ISSN | 0009-9147 |
DOIs | |
Publication status | Published - Nov 2011 |
- Aged, Biomarkers/metabolism, Calcium-Binding Proteins/blood, Cardiovascular Diseases/diagnosis, Carotid Intima-Media Thickness, Case-Control Studies, Diabetes Mellitus, Type 2/complications, Extracellular Matrix/metabolism, Extracellular Matrix Proteins/metabolism, Female, Follow-Up Studies, Humans, Immunoassay, Immunohistochemistry, Male, Mammary Arteries/metabolism, Middle Aged, Oligonucleotide Array Sequence Analysis, Predictive Value of Tests, Prospective Studies, Real-Time Polymerase Chain Reaction
Research areas
ID: 247872524