Dr. Dimitrios Tsiantoulas, PhD
MedUni Wien RESEARCHER OF THE MONTH Oktober 2022
APRIL (A Proliferation Inducing Ligand) is a cytokine produced by many cell subsets such as myeloid and stromal cells. We have demonstrated that genetic deletion or antibody mediated neutralization of APRIL in mice aggravates atherosclerosis. The protective effect of APRIL in atherosclerosis is mediated via binding to arterial heparan sulfate proteoglycans, which are responsible for the retention of LDL cholesterol in the subendothelial space of arteries. Moreover, we provide evidence that APRIL competes for the binding of LDL cholesterol in arterial proteoglycans. Furthermore, we discovered that human serum contains a previously unknown form of APRIL, which we termed non-canonical APRIL. Non-canonical APRIL binds strongly to heparan sulfate proteoglycans, and its circulating levels are independently associated with long-term cardiovascular mortality in patients with atherosclerotic cardiovascular disease.
Selected Literature
- Tsiantoulas D, Eslami M, Obermayer G, Clement M, Smeets D, Mayer FJ, et al. APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans. Nature. 2021;597(7874):92-6.
- Tsiantoulas D, Bot I, Ozsvar-Kozma M, Goderle L, Perkmann T, Hartvigsen K, et al. Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency. Circ Res. 2017;120(1):78-84.
- Tsiantoulas D, Sage AP, Goderle L, Ozsvar-Kozma M, Murphy D, Porsch F, et al. B Cell-Activating Factor Neutralization Aggravates Atherosclerosis. Circulation. 2018;138(20):2263-73.