uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Heparin interactions with apoA1 and SAA in inflammation-associated HDL
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Lund Univ, MAX IV Lab, POB 118, SE-22100 Lund, Sweden..
Biognos AB, Box 8963, Gothenburg, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
2016 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 474, no 2, 309-314 p.Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

Apolipoprotein A1 (apoA1) is the main protein component responsible for transportation of cholesterol on high-density lipoprotein (HDL). Serum amyloid A (SAA) is an acute phase protein associated with HDL. Apart from their physiological functions, both apoA1 and SAA have been identified as 'amyloidogenic peptides'. We report herein that the polysaccharide heparin interacts with both apoA1 and SAA in HDL isolated from plasma of inflamed mice. The reaction is rapid, forming complex aggregates composed of heparin, apoA1 and SAA as revealed by gel electrophoresis. This interaction is dependent on the size and concentration of added heparin. Mass spectrometry analysis of peptides derived from chemically crosslinked HDL-SAA particles detected multiple crosslinks between apoA1 and SAA, indicating close proximity (within 25 angstrom) of these two proteins on the HDL surface, providing a molecular and structural mechanism for the simultaneous binding of heparin to apoA1 and SAA.

Place, publisher, year, edition, pages
2016. Vol. 474, no 2, 309-314 p.
Keyword [en]
Heparan sulfate, Lipoproteins/receptors, Amyloid, Atherosclerosis, Proteoglycans, Mass spectrometry
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-298081DOI: 10.1016/j.bbrc.2016.04.092ISI: 000376221700013PubMedID: 27105909OAI: oai:DiVA.org:uu-298081DiVA: diva2:944792
Funder
Swedish Research Council, K2012-67X-21128-04-4Swedish Heart Lung Foundation, 20140131
Available from: 2016-06-30 Created: 2016-06-29 Last updated: 2017-02-20Bibliographically approved
In thesis
1. Implications of Heparan Sulfate and Heparanase in Inflammatory Diseases
Open this publication in new window or tab >>Implications of Heparan Sulfate and Heparanase in Inflammatory Diseases
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Heparan sulfate (HS), an unbranched sulfated carbohydrate chain, and the HS-degrading enzyme heparanase play important roles in physiological and pathological processes during all stages of life, from early embryogenesis to ageing. Accumulated information shows that HS and heparanase are involved in inflammatory processes and associated diseases, e.g. rheumatoid arthritis (RA) and Alzheimer’s disease.

In this thesis I have investigated the role of HS and heparanase (Hpa) in inflammatory-related pathologies. In the first project, Hpa overexpressing mice (Hpa-tg) were induced with a murine model of RA. We found a pro-inflammatory role of Hpa through enhancing the activity of T-cells and innate immune cells, which contributed to an augmented severity of clinical symptoms in the Hpa-tg mice.

In my second project, we revealed co-current interaction of heparin with both ApoA1 and SAA of HDL isolated from plasma of inflamed mouse. Mass spectrometry analysis indicated close proximity of ApoA1 and SAA on the HDL surface, providing a molecular and structural mechanism for the simultaneous binding of heparin to apoA1 and SAA.

In my third project, we investigated the role of Hpa in AA amyloid formation and resolution in mice in a model of AA-amyloidosis. We found a similar degree of amyloid formation in Hpa-KO mice compared to the wildtype control mice, but the resolution process was faster in Hpa-KO mice. The rapid clearance of deposited SAA in Hpa-KO mice was associated with upregulated expression of matrix metalloproteases. The results suggest an associated function of ECM proteases with heparanase in the process of AA amyloid resolution.

In my fourth project, we found that overexpression of heparanase impaired inflammation associated beta amyloid (Aβ) clearance in the brain of an Alzheimer’s disease mouse model. Examination of the cytokine profile of brain lysates revealed an overall lower inflammatory reaction in the double transgenic (tgHpa*Swe) mice compared to single APP-tg (tg-Swe) mice in response to LPS-induced inflammation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1303
Keyword
Heparanase, Heparan sulfate, Inflammation, Inflammatory diseases, Autoimmune diseases, Amyloidosis, Reumathoid arthritis, SAA, APP, A beta, Neuroinflammation
National Category
Basic Medicine
Research subject
Medical Science; Medical Biochemistry; Immunology; Neurology
Identifiers
urn:nbn:se:uu:diva-315699 (URN)978-91-554-9828-3 (ISBN)
Public defence
2017-04-07, A1:111a, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Funder
Swedish Research Council
Available from: 2017-03-17 Created: 2017-02-20 Last updated: 2017-03-20

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Digre, AndreasLi, Jin-Ping
By organisation
Department of Medical Biochemistry and MicrobiologyScience for Life Laboratory, SciLifeLab
In the same journal
Biochemical and Biophysical Research Communications - BBRC
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 437 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf