TIE receptors as molecular switches between pro-angiogenic or vascular normalizing effects of macrophages.

Angiogenesis, the process of blood vessel development, is an important mechanism in health and
disease. Angiogenesis is extensively being studied as a therapeutic target in conditions where
aberrant blood vessel growth worsens the clinical outcome, such as in atherosclerotic plaque
formation. However, angiogenesis is also being studied as a therapeutic tool to resupply ischemic
tissue with blood vessels. A good knowledge of the factors that regulate blood vessel growth and
maturation are indispensable to design effective treatments that can halt or restore a functional
vascular network.
Here, we will investigate the role of a specific type of immune cells (macrophages) on angiogenesis.
We hypothesize that TIE2 expressing macrophages (TEMs) are both important during initial blood
vessel growth, but also play a role for the subsequent steps of blood vessel expansion, remodeling
and maturation. We hypothesize that this effect is mediated by the TIE2 binding growth factors, the
angiopoietins. The molecular pathway of TIE2 in TEMs has not been well described. We will
investigate how the angiopoietins activate the TIE2 receptor on TEMs and if this is situation
dependent. Furthermore, we will assess whether this affects angiogenesis and especially vascular
maturation. Finally, we will identify the molecular pathways involved in these processes. With the
present project we hope to identify therapeutic targets that can be used to fine-tune angiogenesis
modulating treatment.