Endothelial cells (ECs) are polarised, allowing them to secrete different proteins into both the circulating fluid, and the underlying matrix. However, there is little understanding of how this polarised secretion occurs. Using mass spectrometry, I have examined the role liprin-α1 plays in the secretion of proteins, which had previously been identified to be involved in the secretion of fibronectin from the basolateral surface. I have shown that liprin-α1 affects the polarised secretion of a subset of proteins, particularly those involved in the assembly of the extracellular matrix (ECM) such as collagen-α1 and α2. Previous studies have suggested that atorvastatin treatment has a positive pleiotropic effect upon ECs, reducing the risk of atherosclerosis. I have shown that atorvastatin treatment affected the secretion of certain proteins from both the apical and basolateral surface of the ECs. One major group of proteins affected were proteins involved in the ECM. Dysregulation of the ECM has previously been shown to be involved in the pathogenesis of atherosclerosis. Additionally, atorvastatin treatment increased the apical/basal secretion ratio of some proteins also known to be involved in the pathogenesis of atherosclerosis, including biglycan. However, atorvastatin also increased the apical secretion of protein-glutamine gamma-glutamyltransferase 2, which is known to decrease rupture of atherosclerotic plaques. Whilst my study provides a slight insight into the polarised secretion from ECs and the role atorvastatin treatment may have in patients with atherosclerosis, further research is needed to validate these results.
|Date of Award||29 Sep 2020|
- The University of Bristol
|Supervisor||Harry H Mellor (Supervisor)|