Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • 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
Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease through the Resolvin E1 and ChemR23 Axis.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Show others and affiliations
2020 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 142, p. 776-789Article in journal (Refereed) Published
Abstract [en]

Background: Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) in cardiovascular prevention have been recently demonstrated in a large randomized controlled trial. In addition, n-3 PUFA serve as the substrate for the synthesis of specialized pro-resolving mediators (SPMs), which are known by their potent beneficial anti-inflammatory, pro-resolving and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and SPMs on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA-derived SPMs in relation to the development of AVS. Methods: Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe-/- mice and wire injury in C57BL/6J mice were used as models for mechanistic studies. Results: We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in non-calcified regions compared with calcified regions. LC-MS-MS based lipid mediator lipidomics identified that the n-3 PUFA-derived SPM resolvin E1 (RvE1) was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe-/- mice expressing the Caenorhabditis elegans Fat-1 transgene (Fat-1tgxApoe-/-), which enables the endogenous synthesis of n-3 PUFA, increased valvular n-3 PUFA content, exhibited reduced valve calcification, lower aortic valve leaflet area, increased M2 macrophage polarization and improved echocardiographic parameters. Finally, abrogation of the RvE1 receptor ChemR23 enhanced disease progression, and the beneficial effects of Fat-1tg were abolished in the absence of ChemR23. Conclusions: n-3 PUFA-derived RvE1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression, and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.

Place, publisher, year, edition, pages
2020. Vol. 142, p. 776-789
Keywords [en]
lipid mediators, omega-3, resolution of Inflammation, valvular heart disease
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-46634DOI: 10.1161/CIRCULATIONAHA.119.041868OAI: oai:DiVA.org:ri-46634DiVA, id: diva2:1459802
Available from: 2020-08-20 Created: 2020-08-20 Last updated: 2023-06-05Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Authority records

Sjövall, Peter

Search in DiVA

By author/editor
Sjövall, Peter
By organisation
Chemistry, Biomaterials and Textiles
In the same journal
Circulation
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 59 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • 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