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

Matthew J Harrison, Myriam Chimen, Mohammed Hussain, Asif Jilani Iqbal, Yotis Senis, Gerard Nash, Steve Watson, George Rainger

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
145 Downloads (Pure)

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

Keywords

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

Fingerprint

Dive into the research topics of 'Signalling through Src Family Kinase isoforms is not redundant in models of thrombo-inflammatory vascular disease'. Together they form a unique fingerprint.

Cite this