Heparanase is overexpressed in the diabetic kidney; however, its role and mode of action in diabetic kidney disease remains largely unclear. Method: Applying heparanase-null mice we found that deletion of the heparanase gene protects diabetic mice from diabetic nephropathy (DN). Recombinant heparanase enzyme and a specific heparanase inhibitor (SST0001) were used to explore its mode of action in several in vivo and in vitro models. Results: There is essential involvement of heparanase in the pathogenesis of DN. Deleting the heparanase gene protects diabetic mice from DN and administration of specific heparanase inhibitor decreases the extent of albuminuria. In vitro, heparanase enhances macrophage activation by diabetic milieu components, and thus increases the kidneydamaging properties of macrophages. Conclusion: Our results validate the role of heparanase in DN and reveal the mechanism of heparanase action emphasizing its function in coupling chronic inflammation, macrophage activation and diabetic kidney injury. These findings will help in developing effective strategies to disrupt the heparanasedriven sequence of events in diabetic kidney disease, and in designing novel therapeutic interventions in DN. Sunday, 9 September 2012, 17.00-19 .00, Terrace 1 OFP-13 Oral Free Paper Session Neuropathology OFP-13-001 Microvascular angiogenesis occurs in a subset of only the arteriovenous types of vascular malformations and is more abundant in men than in women L. B. Meijer-Jorna * , C. M. van der Horst, C. M. van der Loos, A. C. van der Wal * Medical Center Alkmaar, Symbiant Pathology Center, Netherlands