| First Author | Harrison MJ | Year | 2018 |
| Journal | J Cell Mol Med | Volume | 22 |
| Issue | 9 | Pages | 4317-4327 |
| PubMed ID | 29974666 | Mgi Jnum | J:289233 |
| Mgi Id | MGI:6434699 | Doi | 10.1111/jcmm.13721 |
| Citation | Harrison MJ, et al. (2018) Signalling through Src family kinase isoforms is not redundant in models of thrombo-inflammatory vascular disease. J Cell Mol Med 22(9):4317-4327 |
| abstractText | The Src family kinases (SFK) are a group of signalling molecules with important regulatory functions in inflammation and haemostasis. Leucocytes and platelets express multiple isoforms of the SFKs. Previous studies used broad-spectrum pharmacological inhibitors, or murine models deficient in multiple SFK isoforms, to demonstrate the functional consequences of deficiencies in SFK signalling. Here, we hypothesized that individual SFK operate in a non-redundant fashion in the thrombo-inflammatory recruitment of monocyte during atherosclerosis. Using in vitro adhesion assays and single SFK knockout mice crossed with the ApoE(-/-) model of atherosclerosis, we find that SFK signalling regulates platelet-dependent recruitment of monocytes. However, loss of a single SFK, Fgr or Lyn, reduced platelet-mediated monocyte recruitment in vitro. This translated into a significant reduction in the burden of atherosclerotic disease in Fgr(-/-) /ApoE(-/-) or Lyn(-/-) /ApoE(-/-) animals. SFK signalling is not redundant in thrombo-inflammatory vascular disease and individual SFK may represent targets for therapeutic intervention. |
