1. Non-related healthy volunteers
N. Pelzer1, R. Bijkerk2,3, M.E.J. Reinders2, A.J. van Zonneveld2,3, M.D. Ferrari 1, A.M.J.M. van den Maagdenberg1,4, J. Eikenboom3,5, G.M. Terwindt1
Departments of 1Neurology, 2Internal Medicine (Nephrology), 3Einthoven Laboratory for Vascular and Regenerative Medicine, 4Human Genetics, 5Internal Medicine, Section Thrombosis and Hemostasis
Leiden University Medical Center, Leiden, the Netherlands
Circulating endothelial markers in the monogenic small vessel disease Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S)
Background
RVCL-S is a monogenic small vessel disease and a model for stroke and vascular dementia
The pathophysiology of RVCL-S is largely unknown but systemic endothelial involvement has been suggested
Here we investigated circulating levels of von Willebrand Factor (VWF) and angiopoietin-2 (Ang-2) to confirm endothelial involvement and to identify biomarkers for disease activity
Conclusions
RVCL-S is an underdiagnosed cerebral hereditary angiopathy
More awareness is needed to prevent harmful unnecessary diagnostics
Increased levels of VWF and Ang-2 confirm RVCL-S is a systemic endotheliopathy and seem early markers of disease activity
Methods
Cross-sectional study in Dutch RVCL-S population
RVCL-S family
confirmed
TREX1 mutation
n= 31
RVCL-S family
without
TREX1 mutation
n= 33
Non-related healthy volunteers
n= 31
Results
Levels of VWF:Ag, VWFpp and Ang-2 were elevated in TREX1 mutation carriers compared to family members without a TREX1 mutation and unrelated healthy controls (p<0.001 for all comparisons)
Most pronounced effects in clinically manifest mutation carriers aged ≥40 years (p<0.001 for all comparisons)
Compared to healthy controls, levels of VWF:Ag (p=0.02) and Ang-2 (p=0.04) were also elevated in mutation carriers aged <40 years.
This work was supported by grants of the Netherlands Organization for Scientific Research (NWO) [VIDI - no to GMT], the Center for Medical Systems Biology (CMSB) established in the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (NGI/NWO) [CMSB - no to AvdM], and the European Community (EC) [FP7-EUROHEADPAIN - no to AvdM & MDF & GMT and FP7-NIMBL - no to AvdM].