Davaapil, H; (2018) The role of the proteoglycans OMD and PRELP in the maintenance of brain vasculature. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

OMD and PRELP are proteoglycans belonging to the family of small leucine-rich repeat proteoglycans (SLRPs), whose members have been shown to modulate a variety of cellular processes, including migration, proliferation and differentiation. Abrogated expression of SLRP members has been linked to a multitude of developmental, age-related and inflammatory diseases. Previous work from the Ohnuma lab has shown that OMD and PRELP are strongly expressed in brain vasculature, and in this study, I aim to extend the understanding of OMD and PRELP in the context of vascular homeostasis. The cellular localisation of OMD and PRELP was investigated and I determined that OMD is weakly expressed in neurons, whereas PRELP is expressed in pericytes, vascular smooth muscle cells, microglia and ependymal cells. I have shown that there is vascular dysfunction in PRELP-/- mice. There is increased blood vessel content in the brain, accompanied by blood brain barrier (BBB) breakdown. Analysis of BBB components indicates basement membrane components laminin and perlecan are down-regulated in addition to coverage by pericytes and astrocyte end-feet. PRELP-/- mice also exhibit weakened adherens- and tight-junctions between endothelial cells. I have determined that OMD-/- brain vasculature is comparable to that of wild-type. I propose that PRELP has a role in maintaining vascular function. PRELP may modulate the stability of the BBB by acting as a bridging molecule for basement membrane proteins.

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