High serum levels of sclerostin and Dickkopf-1 are associated with acute ischaemic stroke

Atherosclerosis. 2016 Oct:253:22-28. doi: 10.1016/j.atherosclerosis.2016.08.003. Epub 2016 Aug 18.

Abstract

Background and aims: Sclerostin and Dickkopf-1 (Dkk-1) are potent antagonists of Wnt signalling and might therefore play important roles in cardiovascular disease. We investigated whether serum sclerostin and Dkk-1 levels are associated with acute ischaemic stroke and specific stroke subtypes.

Methods: Serum levels of sclerostin and Dkk-1 were measured by ELISA on day 1 and on day 6 after stroke in 62 patients with large artery atherosclerotic (LAA) stroke, on day 1 after stroke in 62 age- and gender-matched patients with small-artery occlusion (SAO) stroke and on admission in 62 healthy controls. Stroke severity was determined based on the National Institutes of Health Stroke Scale (NIHSS) and by measuring stroke volume on diffusion-weighted imaging. Outcome was measured by the modified Rankin Scale (mRS) on day 90.

Results: Compared with controls, serum sclerostin and Dkk-1 levels were significantly higher in both patients with LAA stroke and with SAO stroke, and no difference was detected between the stroke subtypes. Sclerostin and Dkk-1 levels remained stable between the first and sixth day after stroke in the patients with LAA stroke. Receiver operating characteristic curve analysis was used to evaluate sclerostin and Dkk-1 as markers of a high risk of stroke and produced area under curve values of 0.773 and 0.776. Adjusted logistic regression showed that serum sclerostin and Dkk-1 levels remained as independent markers of stroke. No correlations were found between sclerostin or Dkk-1 levels and stroke severity or stroke outcome.

Conclusions: High serum levels of sclerostin and Dkk-1 are associated with acute ischaemic stroke.

Keywords: Dickkopf-1; Ischaemic stroke; Sclerostin; Wnt pathways.

MeSH terms

  • Acute Disease
  • Adaptor Proteins, Signal Transducing
  • Aged
  • Area Under Curve
  • Atherosclerosis / physiopathology
  • Blood Pressure
  • Bone Morphogenetic Proteins / blood*
  • Brain Ischemia / blood*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Markers
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Male
  • Middle Aged
  • Regression Analysis
  • Reproducibility of Results
  • Signal Transduction
  • Stroke / blood*
  • Time Factors
  • Wnt Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Bone Morphogenetic Proteins
  • DKK1 protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • SOST protein, human
  • Wnt Proteins