Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

  • Claudia Cangemi
  • Vibe Skov
  • Michael Kjaer Poulsen
  • Jonas Funder
  • Waleed O Twal
  • Mari-Anne Gall
  • Hjortdal, Vibeke Elisabeth
  • Marie Louise Jespersen
  • Torben A Kruse
  • Jan Aagard
  • Hans-Henrik Parving
  • Steen Knudsen
  • Poul-Flemming Høilund-Carlsen
  • Rossing, Peter
  • Jan Erik Henriksen
  • William Scott Argraves
  • Lars Melholt Rasmussen

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.

OriginalsprogEngelsk
TidsskriftClinical Chemistry
Vol/bind57
Udgave nummer11
Sider (fra-til)1556-65
Antal sider10
ISSN0009-9147
DOI
StatusUdgivet - nov. 2011

ID: 247872524