Circulating Dickkopf-1 in acute ischemic stroke and clinically stable cerebrovascular disease

Previous data suggest that Dickkopf-1 (Dkk-1), an inhibitor of the canonical/β-catenin cascade of the Wnt pathway, is upregulated in carotid atherosclerosis and acute myocardial ischemia. It is currently unclear if such upregulation also occurs in cerebral ischemia.

We measured plasma levels of Dkk-1 in patients with acute ischemic stroke (n=57) within 24h from symptom onset, in patients with clinically stable cerebrovascular disease (n=29) and in healthy controls (n=29). Stroke severity on admission was determined by the National Institutes of Stroke Scale (NIHSS). The modified Rankin Scale (mRS) served to define outcome at day 90. Ischemic stroke subtype and cause was determined by the Oxfordshire Community Stroke Project (OCSP) criteria and the Causative Classification of Stroke System (CCS).

Dkk-1 plasma levels were significantly higher in acute stroke patients (median 727.1 pg/ml) as compared to patients with stable cerebrovascular disease (median 534.2 pg/ml; p=0.017) or healthy controls (median 371.3 pg/ml; p<0.001). The difference of Dkk-1 levels between patients with stable cerebrovascular disease and healthy controls was also significant (p=0.005). No significant differences in Dkk-1 plasma levels were found between different causes or subtypes of ischemic stroke. No correlation of Dkk-1 levels was found with stroke severity on admission and outcome at day 90.

Our study provides for the first time evidence for a release of Dkk-1 into the circulation in patients with acute ischemic stroke and also in patients with clinically stable cerebrovascular disease.