Vascular adhesion protein-1, its ligands and role in cardiovascular disease prediction




Santalahti Kristiina

PublisherUniversity of Turku

Turku

2018

978-951-29-7323-1

978-951-29-7324-8

http://urn.fi/URN:ISBN:978-951-29-7324-8(external)

http://urn.fi/URN:ISBN:978-951-29-7324-8(external)



To study the pathogenesis and prevention of diseases, population studies in which hundreds of measurements are done from the same persons have a crucial role. A biomarker is any measurable characteristic that gives information on the biological state of the body. At its best a biomarker can predict future disease events. Cardiovascular diseases (CVDs) are chronic diseases in which one feature is harmful leukocyte trafficking. 

In this thesis project, I studied vascular adhesion protein-1 (VAP-1), a molecule involved in leukocyte trafficking. I wanted to identify the ligands on the surface of leukocytes to which VAP-1 binds to and thus helps the leukocytes to migrate from blood to tissues. A soluble form of VAP-1 (sVAP-1) is present in the blood. To study sVAP-1 as a biomarker, I developed two different assays to measure the sVAP-1 levels in a high throughput way. This enabled the measurements of the sVAP-1 levels in two population cohorts and examine whether sVAP-1 associates with early phases of CVDs. Furthermore, I investigated the ability of sVAP-1 levels to predict future cardiovascular events in a Finnish population. 

In this thesis, the first leukocyte ligands for VAP-1 were identified. Sialic acid binding Ig-like lectins Siglec-10 and Siglec-9 are expressed on different leukocytes and were able to bind to VAP-1. In addition, the sVAP-1 levels from nearly 5000 Finns were measured with the newly developed assays. The statistical analyses revealed that increased levels of serum sVAP-1 correlated with early manifestations of atherosclerosis. Additionally, sVAP-1 levels could predict future cardiovascular events and even improved the reclassification of patients to correct risk categories.



Last updated on 2024-03-12 at 13:03