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The Vascular Repair Process after Injury of the Carotid Artery is regulated by IL-1RI and MyD88 Signalling.

Saxena, Amit LU ; Rauch, Uwe LU ; Berg, Katarina LU ; Andersson, Linda LU ; Hollender, Lisette LU ; Carlsson, Ann-Margreth LU ; Gomez, Maria LU ; Nilsson, Anna Hultgårdh; Nilsson, Jan LU and Björkbacka, Harry LU (2011) In Cardiovascular Research 91. p.350-357
Abstract
Aim: The aim of this study was to determine if innate immune signalling influences the vascular repair process in response to mechanical injury of arteries in mice. Methods and Results: A non-obstructive collar was introduced around the carotid artery of MyD88-deficient mice and neointima formation was compared to that observed in MyD88-competent mice. MyD88-deficient mice are characterized by impaired signal transduction from interleukin (IL)-1/IL-18 receptors and most Toll-like receptors. The vascular response to injury was severely impaired in MyD88-deficient mice as neointima formation was not different from sham operated mice, whereas MyD88-competent mice displayed robust neointima formation. Furthermore, infiltration of CD68 positive... (More)
Aim: The aim of this study was to determine if innate immune signalling influences the vascular repair process in response to mechanical injury of arteries in mice. Methods and Results: A non-obstructive collar was introduced around the carotid artery of MyD88-deficient mice and neointima formation was compared to that observed in MyD88-competent mice. MyD88-deficient mice are characterized by impaired signal transduction from interleukin (IL)-1/IL-18 receptors and most Toll-like receptors. The vascular response to injury was severely impaired in MyD88-deficient mice as neointima formation was not different from sham operated mice, whereas MyD88-competent mice displayed robust neointima formation. Furthermore, infiltration of CD68 positive leukocytes was dependent on MyD88. During the early response to injury, 3 days after collar placement, a transient increase in the expression of Toll-like receptor (TLR) 4 on vascular smooth muscle cells was observed. To determine the relative importance of IL-1 receptor and TLR4 activation in the vascular response to injury mice were injected with blocking antibodies to these receptors prior to the collar placement. Neointima formation was reduced by 80% in mice administered IL-1RI blocking antibodies compared to mice given a control antibody, whereas administration of TLR4 blocking antibodies was without effect. Conclusion: These results show that inhibition of MyD88- or IL-1 receptor signalling reduces neointima formation in response to vascular injury and could offer therapeutic options for reducing clinical complications of excessive smooth muscle cell proliferation, such as that observed in in-stent restenosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cardiovascular Research
volume
91
pages
350 - 357
publisher
Elsevier
external identifiers
  • wos:000292338600019
  • pmid:21421554
  • scopus:79959965458
ISSN
1755-3245
DOI
10.1093/cvr/cvr075
language
English
LU publication?
yes
id
437c5ddd-9ec4-4338-aa87-613e7f52fcd1 (old id 1883678)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21421554?dopt=Abstract
date added to LUP
2011-04-01 17:22:50
date last changed
2017-06-25 04:36:27
@article{437c5ddd-9ec4-4338-aa87-613e7f52fcd1,
  abstract     = {Aim: The aim of this study was to determine if innate immune signalling influences the vascular repair process in response to mechanical injury of arteries in mice. Methods and Results: A non-obstructive collar was introduced around the carotid artery of MyD88-deficient mice and neointima formation was compared to that observed in MyD88-competent mice. MyD88-deficient mice are characterized by impaired signal transduction from interleukin (IL)-1/IL-18 receptors and most Toll-like receptors. The vascular response to injury was severely impaired in MyD88-deficient mice as neointima formation was not different from sham operated mice, whereas MyD88-competent mice displayed robust neointima formation. Furthermore, infiltration of CD68 positive leukocytes was dependent on MyD88. During the early response to injury, 3 days after collar placement, a transient increase in the expression of Toll-like receptor (TLR) 4 on vascular smooth muscle cells was observed. To determine the relative importance of IL-1 receptor and TLR4 activation in the vascular response to injury mice were injected with blocking antibodies to these receptors prior to the collar placement. Neointima formation was reduced by 80% in mice administered IL-1RI blocking antibodies compared to mice given a control antibody, whereas administration of TLR4 blocking antibodies was without effect. Conclusion: These results show that inhibition of MyD88- or IL-1 receptor signalling reduces neointima formation in response to vascular injury and could offer therapeutic options for reducing clinical complications of excessive smooth muscle cell proliferation, such as that observed in in-stent restenosis.},
  author       = {Saxena, Amit and Rauch, Uwe and Berg, Katarina and Andersson, Linda and Hollender, Lisette and Carlsson, Ann-Margreth and Gomez, Maria and Nilsson, Anna Hultgårdh and Nilsson, Jan and Björkbacka, Harry},
  issn         = {1755-3245},
  language     = {eng},
  pages        = {350--357},
  publisher    = {Elsevier},
  series       = {Cardiovascular Research},
  title        = {The Vascular Repair Process after Injury of the Carotid Artery is regulated by IL-1RI and MyD88 Signalling.},
  url          = {http://dx.doi.org/10.1093/cvr/cvr075},
  volume       = {91},
  year         = {2011},
}