title: The vascular repair process after injury of the carotid artery is regulated by IL-1RI and MyD88 signalling.
abstract: OBJECTIVE
  The aim of this study was to determine whether innate immune signalling influences the vascular repair process in response to mechanical injury of arteries in mice.
  
  
  RESULTS
  A non-obstructive collar was introduced around the carotid artery of MyD88-deficient mice, and neointima formation was compared with 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 (TLRs). 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 leucocytes was dependent on MyD88. During the early response to injury, 3 days after collar placement, a transient increase in the expression of TLR4 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 with mice given a control antibody, whereas administration of TLR4 blocking antibodies was without effect.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental Medicine, Lund University, Lund, Sweden.
authors.forename: Amit
authors.initials: A
authors.lastname: Saxena
authors.forename: Uwe
authors.initials: U
authors.lastname: Rauch
authors.forename: Katarina E
authors.initials: KE
authors.lastname: Berg
authors.forename: Linda
authors.initials: L
authors.lastname: Andersson
authors.forename: Lisette
authors.initials: L
authors.lastname: Hollender
authors.forename: Ann-Margreth
authors.initials: AM
authors.lastname: Carlsson
authors.forename: Maria F
authors.initials: MF
authors.lastname: Gomez
authors.forename: Anna
authors.initials: A
authors.lastname: Hultgårdh-Nilsson
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.forename: Harry
authors.initials: H
authors.lastname: Björkbacka
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000187:drug effects; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017539:Tunica Intima / Q000276:immunology / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053594:Myeloid Differentiation Factor 88; D053573:Receptors, Interleukin-1 Type I; D051197:Toll-Like Receptor 4; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C507780:Myd88 protein, mouse; C493487:Tlr4 protein, mouse