Defining differential role(s) of the TAM receptor 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, we have demonstrated increased atherosclerosis in Axl-/- mice with a switch versus a less contractile smooth muscle cell phenotype.

We 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.