| http://purl.uniprot.org/citations/34433968 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34433968 | http://www.w3.org/2000/01/rdf-schema#comment | "Atherosclerotic cardiovascular disease causes heart attacks and strokes, which are the leading causes of mortality worldwide1. The formation of atherosclerotic plaques is initiated when low-density lipoproteins bind to heparan-sulfate proteoglycans (HSPGs)2 and become trapped in the subendothelial space of large and medium size arteries, which leads to chronic inflammation and remodelling of the artery wall2. A proliferation-inducing ligand (APRIL) is a cytokine that binds to HSPGs3, but the physiology of this interaction is largely unknown. Here we show that genetic ablation or antibody-mediated depletion of APRIL aggravates atherosclerosis in mice. Mechanistically, we demonstrate that APRIL confers atheroprotection by binding to heparan sulfate chains of heparan-sulfate proteoglycan 2 (HSPG2), which limits the retention of low-density lipoproteins, accumulation of macrophages and formation of necrotic cores. Indeed, antibody-mediated depletion of APRIL in mice expressing heparan sulfate-deficient HSPG2 had no effect on the development of atherosclerosis. 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 we termed non-canonical APRIL (nc-APRIL), are associated independently of traditional risk factors with long-term cardiovascular mortality in patients with atherosclerosis. Our data reveal properties of APRIL that have broad pathophysiological implications for vascular homeostasis."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41586-021-03818-3"xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Clement M."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Mueller A."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Donze O."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Schneider P."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Murphy J.E."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Marz W."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Scharnagl H."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Smeets D."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Simon T."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Willen L."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Hess H."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Lambert J."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Kubicek S."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Boren J."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Pasterkamp G."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Binder C.J."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Mallat Z."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Eslami M."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Enders L."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Hoke M."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Afonyushkin T."xsd:string |
| http://purl.uniprot.org/citations/34433968 | http://purl.uniprot.org/core/author | "Fogelstrand P."xsd:string |