| First Author | Saxena A | Year | 2011 |
| Journal | Cardiovasc Res | Volume | 91 |
| Issue | 2 | Pages | 350-7 |
| PubMed ID | 21421554 | Mgi Jnum | J:191559 |
| Mgi Id | MGI:5462040 | Doi | 10.1093/cvr/cvr075 |
| Citation | Saxena A, et al. (2011) The vascular repair process after injury of the carotid artery is regulated by IL-1RI and MyD88 signalling. Cardiovasc Res 91(2):350-7 |
| abstractText | AIM: 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. METHODS AND 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. 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. |
