Introduction: Eph receptors (Ephs) and their ephrin ligands are related to a plethora of physiological and pathological processes including atherosclerosis. Preliminary data of our lab showed EphB2 to be the most abundantly expressed Eph receptor on monocytes, one of the culprit cell types in atherosclerosis. Combined with the observation that the EphB2 receptor gene is located on a myocardial infarction locus, we hypothesized that monocytic EphB2 plays a role in atherosclerosis and we investigated the expression and function of EphB2 in human atherosclerosis. 

Methods: Human aortic sections with varying stages of atherosclerosis were stained for EphB2 and its ephrinB ligands. In vitro activation and silencing of EphB2 in monocytes enabled us to investigate the role of EphB2 in the monocyte-endothelial interaction.

Results: In atherosclerotic plaque stainings, a proportional increase of EphB2 receptor and ephrinB ligands protein was observed with plaque progression. Functionally, we have shown that activation of monocytic EphB2 via exposure to recombinant ephrinB1/B2 did not alter monocyte-to-endothelial cell adhesion and transmembrane migration. Importantly, monocytes with reduced levels of EphB2 showed a significant decrease in adhesion and migration and showed alterations in the (regulation of the) cellular cytoskeleton.

Conclusion: We have shown that expression of EphB2 and its ligands ephrinB in atherosclerotic lesions is driven by atherosclerosis progression. In addition we have shown that EphB2 facilitates, ligand independently, monocyte adhesion and migration potentially via regulation of the cytoskeleton of the cells, which in vivo might promote monocyte accumulation and thereby atherogenesis.

04 - EXPRESSION AND FUNCTION OF EPHRIN RECEPTOR B2 IN HUMAN ATHEROSCLEROSIS: AN LIGAND INDEPENDENT GUIDANCE CUE