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APRIL limits athero...
APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans
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Tsiantoulas, D. (author)
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Eslami, M. (author)
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Obermayer, G. (author)
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show more...
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Clement, M. (author)
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Smeets, D. (author)
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Mayer, F. J. (author)
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Kiss, M. G. (author)
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Enders, L. (author)
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Weisser, J. (author)
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Goderle, L. (author)
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Lambert, J. (author)
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Frommlet, F. (author)
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Mueller, A. (author)
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Hendrikx, T. (author)
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Ozsvar-Kozma, M. (author)
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Porsch, F. (author)
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Willen, L. (author)
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Afonyushkin, T. (author)
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Murphy, J. E. (author)
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- Fogelstrand, Per, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
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Donze, O. (author)
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Pasterkamp, G. (author)
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Hoke, M. (author)
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Kubicek, S. (author)
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Jorgensen, H. F. (author)
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Danchin, N. (author)
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Simon, T. (author)
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Scharnagl, H. (author)
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Marz, W. (author)
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
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Hess, H. (author)
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Mallat, Z. (author)
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Schneider, P. (author)
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Binder, C. J. (author)
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(creator_code:org_t)
- 2021-08-25
- 2021
- English.
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597, s. 92-96
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- sample preparation
- taci
- activation
- antibodies
- perlecan
- roles
- cells
- Science & Technology - Other Topics
Publication and Content Type
- ref (subject category)
- art (subject category)
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Nature
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
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Tsiantoulas, D.
-
Eslami, M.
-
Obermayer, G.
-
Clement, M.
-
Smeets, D.
-
Mayer, F. J.
-
show more...
-
Kiss, M. G.
-
Enders, L.
-
Weisser, J.
-
Goderle, L.
-
Lambert, J.
-
Frommlet, F.
-
Mueller, A.
-
Hendrikx, T.
-
Ozsvar-Kozma, M.
-
Porsch, F.
-
Willen, L.
-
Afonyushkin, T.
-
Murphy, J. E.
-
Fogelstrand, Per ...
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Donze, O.
-
Pasterkamp, G.
-
Hoke, M.
-
Kubicek, S.
-
Jorgensen, H. F.
-
Danchin, N.
-
Simon, T.
-
Scharnagl, H.
-
Marz, W.
-
Borén, Jan, 1963
-
Hess, H.
-
Mallat, Z.
-
Schneider, P.
-
Binder, C. J.
-
show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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Nature
- By the university
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University of Gothenburg