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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04414naa a2200781 4500 | |
| 001 | oai:gup.ub.gu.se/307677 | |
| 003 | SwePub | |
| 008 | 240528s2021 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://gup.ub.gu.se/publication/3076772 URI |
| 024 | 7 | a https://doi.org/10.1038/s41586-021-03818-32 DOI |
| 040 | a (SwePub)gu | |
| 041 | a eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Tsiantoulas, D.4 aut |
| 245 | 1 0 | a APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans |
| 264 | c 2021-08-25 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2021 |
| 520 | a Atherosclerotic cardiovascular disease causes heart attacks and strokes, which are the leading causes of mortality worldwide(1). 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 wall(2). A proliferation-inducing ligand (APRIL) is a cytokine that binds to HSPGs(3), 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. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng |
| 653 | a sample preparation | |
| 653 | a taci | |
| 653 | a activation | |
| 653 | a antibodies | |
| 653 | a perlecan | |
| 653 | a roles | |
| 653 | a cells | |
| 653 | a Science & Technology - Other Topics | |
| 700 | 1 | a Eslami, M.4 aut |
| 700 | 1 | a Obermayer, G.4 aut |
| 700 | 1 | a Clement, M.4 aut |
| 700 | 1 | a Smeets, D.4 aut |
| 700 | 1 | a Mayer, F. J.4 aut |
| 700 | 1 | a Kiss, M. G.4 aut |
| 700 | 1 | a Enders, L.4 aut |
| 700 | 1 | a Weisser, J.4 aut |
| 700 | 1 | a Goderle, L.4 aut |
| 700 | 1 | a Lambert, J.4 aut |
| 700 | 1 | a Frommlet, F.4 aut |
| 700 | 1 | a Mueller, A.4 aut |
| 700 | 1 | a Hendrikx, T.4 aut |
| 700 | 1 | a Ozsvar-Kozma, M.4 aut |
| 700 | 1 | a Porsch, F.4 aut |
| 700 | 1 | a Willen, L.4 aut |
| 700 | 1 | a Afonyushkin, T.4 aut |
| 700 | 1 | a Murphy, J. E.4 aut |
| 700 | 1 | a Fogelstrand, Per,d 1971u Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine4 aut0 (Swepub:gu)xfogpe |
| 700 | 1 | a Donze, O.4 aut |
| 700 | 1 | a Pasterkamp, G.4 aut |
| 700 | 1 | a Hoke, M.4 aut |
| 700 | 1 | a Kubicek, S.4 aut |
| 700 | 1 | a Jorgensen, H. F.4 aut |
| 700 | 1 | a Danchin, N.4 aut |
| 700 | 1 | a Simon, T.4 aut |
| 700 | 1 | a Scharnagl, H.4 aut |
| 700 | 1 | a Marz, W.4 aut |
| 700 | 1 | a Borén, Jan,d 1963u Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine4 aut0 (Swepub:gu)xborej |
| 700 | 1 | a Hess, H.4 aut |
| 700 | 1 | a Mallat, Z.4 aut |
| 700 | 1 | a Schneider, P.4 aut |
| 700 | 1 | a Binder, C. J.4 aut |
| 710 | 2 | a Göteborgs universitetb Institutionen för medicin4 org |
| 773 | 0 | t Natured : Springer Science and Business Media LLCg 597, s. 92-96q 597<92-96x 0028-0836x 1476-4687 |
| 856 | 4 | u https://serval.unil.ch/resource/serval:BIB_17F331130FAD.P002/REF.pdf |
| 856 | 4 8 | u https://gup.ub.gu.se/publication/307677 |
| 856 | 4 8 | u https://doi.org/10.1038/s41586-021-03818-3 |
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