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Heparan sulfate pro...
Heparan sulfate proteoglycans present PCSK9 to the LDL receptor
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- Gustafsen, Camilla (författare)
- Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark.
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- Olsen, Ditte (författare)
- Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark.
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- Vilstrup, Joachim (författare)
- Aarhus Univ, Dept Mol Biol & Genet, Gustav Wieds Vej 10, DK-8000 Aarhus, Denmark.
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- Lund, Signe (författare)
- Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark.
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- Reinhardt, Anika (författare)
- Scienion AG, Volmerstr 7b, D-12489 Berlin, Germany.
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- Wellner, Niels (författare)
- Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark.
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- Larsen, Torben (författare)
- Aarhus Univ, Dept Anim Sci, Blichers Alle 20, DK-8830 Tjele, Denmark.
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- Andersen, Christian B. F. (författare)
- Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark.
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- Weyer, Kathrin (författare)
- Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark.
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- Li, Jin-Ping (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Seeberger, Peter H. (författare)
- Max Planck Inst Colloids & Interfaces, Dept Biomol Syst, Muhlenberg 1 OT Golm, D-14476 Potsdam, Germany.
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- Thirup, Soren (författare)
- Aarhus Univ, Dept Mol Biol & Genet, Gustav Wieds Vej 10, DK-8000 Aarhus, Denmark.
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- Madsen, Peder (författare)
- Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark.
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- Glerup, Simon (författare)
- Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark.
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Aarhus Univ, Dept Biomed, Ole Worms Alle 3, DK-8000 Aarhus, Denmark Aarhus Univ, Dept Mol Biol & Genet, Gustav Wieds Vej 10, DK-8000 Aarhus, Denmark. (creator_code:org_t)
- 2017-09-11
- 2017
- Engelska.
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats. Accordingly, heparan sulfate mimetics and monoclonal antibodies directed against the heparan sulfate-binding site are potent PCSK9 inhibitors. We propose that heparan sulfate proteoglycans lining the hepatocyte surface capture PCSK9 and facilitates subsequent PCSK9: LDLR complex formation. Our findings provide new insights into LDL biology and show that targeting PCSK9 using heparan sulfate mimetics is a potential therapeutic strategy in coronary artery disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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- Av författaren/redakt...
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Gustafsen, Camil ...
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Olsen, Ditte
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Vilstrup, Joachi ...
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Lund, Signe
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Reinhardt, Anika
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Wellner, Niels
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visa fler...
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Larsen, Torben
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Andersen, Christ ...
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Weyer, Kathrin
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Li, Jin-Ping
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Seeberger, Peter ...
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Thirup, Soren
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Madsen, Peder
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Glerup, Simon
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visa färre...
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