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ludc webb

Harry Björkbacka

Researcher

ludc webb

Rip2 Deficiency Leads to Increased Atherosclerosis Despite Decreased Inflammation.

Author

  • Malin C Levin
  • Pernilla Jirholt
  • Anna Wramstedt
  • Maria E Johansson
  • Anna M Lundberg
  • Maria Gustafsson Trajkovska
  • Marcus Ståhlman
  • Per Fogelstrand
  • Mikael Brisslert
  • Linda Fogelstrand
  • Zhong-Qun Yan
  • Göran K Hansson
  • Harry Björkbacka
  • Sven-Olof Olofsson
  • Jan Borén

Summary, in English

Rationale:The innate immune system and in particular the pattern-recognition receptors Toll-like receptors have recently been linked to atherosclerosis. Consequently, inhibition of various signaling molecules downstream of the Toll-like receptors has been tested as a strategy to prevent progression of atherosclerosis. Receptor-interacting protein 2 (Rip2) is a serine/threonine kinase that is involved in multiple nuclear factor-κB (NFκB) activation pathways, including Toll-like receptors, and is therefore an interesting potential target for pharmaceutical intervention.Objective:We hypothesized that inhibition of Rip2 would protect against development of atherosclerosis.Methods and Results:Surprisingly, and contrary to our hypothesis, we found that mice transplanted with Rip2(-/-) bone marrow displayed markedly increased atherosclerotic lesions despite impaired local and systemic inflammation. Moreover, lipid uptake was increased, whereas immune signaling was reduced in Rip2(-/-) macrophages. Further analysis in Rip2(-/-) macrophages showed that the lipid accumulation was scavenger-receptor independent and mediated by Toll-like receptor 4 (TLR4)-dependent lipid uptake.Conclusions:Our data show that lipid accumulation and inflammation are dissociated in the vessel wall in mice with Rip2(-/-) macrophages. These results for the first time identify Rip2 as a key regulator of cellular lipid metabolism and cardiovascular disease.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2011

Language

English

Pages

50-1210

Publication/Series

Circulation Research

Volume

109

Document type

Journal article

Publisher

American Heart Association

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1524-4571