Defining differential roles of the TAM receptor Axl in atherosclerosis
Published: 12 April 2021
Dr Pasquale Maffia, Dr Mariola Kurowska-Stolarska and Professor Tomasz Guzik (ICAMS) were recently awarded a project grant from the British Heart Foundation (BHF) that will allow the team to continue their research into Axl in atherosclerosis.
Institute scientists Dr Pasquale Maffia and Dr Mariola Kurowska-Stolarska were recently awarded a project grant from the British Heart Foundation (BHF).
The funding will allow the team, which includes Professor Tomasz Guzik (ICAMS) with Lucy McShane the named postdoc, to continue their research into Axl in atherosclerosis.
The TAM receptors are a distinct family of three receptor tyrosine kinases, namely Tyro3, Axl and MerTK, which play critical roles in cancer, inflammatory disorders and cardiovascular diseases.
Axl, in particular, has been shown to influence multiple aspects of cardiovascular pathology via diverse effects on cells of both the vasculature and immune system through regulation of vascular remodelling, efferocytosis and inflammation.
Clinical studies have shown that Axl is detectable in atherosclerotic plaques; however, the causal relationship between Axl and atherosclerosis is still uncertain, and results from mouse models fell short of defining the specific role(s) of Axl in the disease process.
In preliminary experiments, the team have demonstrated increased atherosclerosis in Axl-/- mice with a switch versus a less contractile smooth muscle cell phenotype. They have also shown a significant reduction of Axl RNA expression in endarterectomy samples compared to healthy control vessels.
These data support the hypothesis of a beneficial role of Axl in atherosclerosis via modulation of smooth muscle cell phenotype/function.
We will now use transcriptomics, in vitro assays, mouse models, and access to human plaque cohorts to precisely address the impact of Axl in atherosclerosis formation and plaque instability, elucidating its potential role as a therapeutic target.
The team are excited to further develop collaborations with Dr Thomas Otto locally, Dr Peder Olofsson and Dr Gabrielle Paulsson-Berne (Karolinska Institutet in Stockholm), Professor Claudia Monaco (Kennedy Institute of Rheumatology in Oxford), Professor Karlheinz Peter and Dr Jonathan Noonan (Baker Heart and Diabetes Institute in Melbourne) and Dr Helle Jørgensen (University of Cambridge) to fulfil the objectives of the grant.
First published: 12 April 2021