The CXCL2 chemokine promotes VEGF-A-regulated angiogenesis

Angiogenesis is the phenomenon of blood vessels sprouting from pre-existing ones.

This can be caused by certain soluble or membrane-bound factors which activate the endothelium which lines all blood vessels.

Atherosclerosis can cause a thrombus or blood clot formation in major arteries which leads to damaged blood vessels and tissues.

A long-standing problem in treating such patients is how to re-establish oxygenated blood supply to tissues such as the heart, limbs and brain. One solution is to harness endothelial cells to promote angiogenesis by developing new collateral blood vessels.

Our pilot work shows that the CXCL2 chemokine supports vascular endothelial growth factor A (VEGF-A)-regulated pro-angiogenic responses.

Our hypothesis is that CXCL2 binds to a G-protein-coupled receptor (CXCR2) on endothelial cells and promotes VEGF-A-regulated angiogenesis.

We will compare the effect of several CXCL chemokines that act as CXCR2 ligands in the regulation of CXCR2-mediated signal transduction linked to endothelial cell migration and tubulogenesis.

Using a mouse hind limb ischaemia model, we will administer CXCL chemokines or a CXCR2 antagonist to assess effects on re-vascularisation.

By establishing a mechanistic basis for CXCL2 in promoting VEGF-A-regulated endothelial function, we can translate this towards vascular therapy.