Signalling through Src Family Kinase isoforms is not redundant in models of thrombo-inflammatory vascular disease

Research output: Contribution to journalArticle

Colleges, School and Institutes

Abstract

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.

Details

Original languageEnglish
Pages (from-to)4317-4327
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume22
Issue number9
Publication statusPublished - 4 Jul 2018

Keywords

  • Atherosclerosis, Inflammation, monocytes, Platelets, Src family kinases