New publication in Nature

In collaboration with international partners of the Universities Lausanne and Cambridge, a study group from the Medical University of Vienna (Department of Laboratory Medicine) could show that genetic ablation or antibody-mediated depletion of a proliferation-inducing ligand (termed APRIL) aggravates atherosclerosis in mice. Christoph Binder's group could demonstrate that APRIL confers atheroprotection by binding to heparan sulfate chains of heparan-sulfate proteoglycan 2 (HSPG2). This limits the retention of low-density lipoproteins, accumulation of macrophages and formation of necrotic cores. Treatment with a specific anti-APRIL antibody that promotes the binding of APRIL to HSPGs reduced experimental atherosclerosis. Furthermore, the serum levels of a form of human APRIL protein that binds to HSPGs, which was termed non-canonical APRIL (nc-APRIL), are associated independently of traditional risk factors with long-term cardiovascular mortality in patients with atherosclerosis. The data, which has now been published in leading journal "Nature", reveal properties of APRIL that have broad pathophysiological implications for vascular homeostasis.  Future studies will investigate the therapeutic value of targeting APRIL in atherosclerotic cardiovascular disease.

Service: Nature

"APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans.” Dimitrios Tsiantoulas, Mahya Eslami, Georg Obermayer, Marc Clement, Diede Smeets, Florian J. Mayer, Máté G. Kiss, Lennart Enders, Juliane Weißer, Laura Göderle, Jordi Lambert, Florian Frommlet, André Mueller, Tim Hendrikx, Maria Ozsvar-Kozma, Florentina Porsch, Laure Willen, Taras Afonyushkin, Jane E. Murphy, Per Fogelstrand, Olivier Donzé, Gerard Pasterkamp, Matthias Hoke, Stefan Kubicek, Helle F. Jörgensen, Nicolas Danchin, Tabassome, Simon, Hubert Scharnagl, Winfried März, Jan Borén, Henry Hess, Ziad Mallat, Pascal Schneider, Christoph J. Binder. DOI: www.nature.com/articles/s41586-021-03818-3