Rip2 Deficiency Leads to Increased Atherosclerosis Despite Decreased Inflammation.
(2011) In Circulation Research 109. p.50-1210- Abstract
- 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... (More)
- 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. (Less)
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https://lup.lub.lu.se/record/2200958
- author
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Circulation Research
- volume
- 109
- pages
- 50 - 1210
- publisher
- American Heart Association
- external identifiers
-
- wos:000296872200008
- pmid:21959219
- scopus:81355160558
- ISSN
- 1524-4571
- DOI
- 10.1161/CIRCRESAHA.111.246702
- language
- English
- LU publication?
- yes
- id
- e589d9eb-85a2-4e10-8e39-739a66fca23c (old id 2200958)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21959219?dopt=Abstract
- date added to LUP
- 2016-04-04 09:13:17
- date last changed
- 2022-01-29 08:50:00
@article{e589d9eb-85a2-4e10-8e39-739a66fca23c, abstract = {{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.}}, author = {{Levin, Malin C and Jirholt, Pernilla and Wramstedt, Anna and Johansson, Maria E and Lundberg, Anna M and Gustafsson Trajkovska, Maria and Ståhlman, Marcus and Fogelstrand, Per and Brisslert, Mikael and Fogelstrand, Linda and Yan, Zhong-Qun and Hansson, Göran K and Björkbacka, Harry and Olofsson, Sven-Olof and Borén, Jan}}, issn = {{1524-4571}}, language = {{eng}}, pages = {{50--1210}}, publisher = {{American Heart Association}}, series = {{Circulation Research}}, title = {{Rip2 Deficiency Leads to Increased Atherosclerosis Despite Decreased Inflammation.}}, url = {{http://dx.doi.org/10.1161/CIRCRESAHA.111.246702}}, doi = {{10.1161/CIRCRESAHA.111.246702}}, volume = {{109}}, year = {{2011}}, }