PLVAP plays a critical role in mediating liver endothelial barrier function in the setting of chronic liver disease (360G-Wellcome-211557_Z_18_Z)

Chronic liver disease (CLD), irrespective of aetiology, follows a common pathway of persistent tissue injury leading to infiltration of immune cells into liver tissue which drives organ fibrosis. There are no medical therapies for end-stage fibrosis, and understanding novel regulatory pathways could lead to urgently needed therapeutic targets for CLD. One such regulatory pathway could be mediated by the interaction between lymphocytes and plasmalemma vesicle associated proteins (PLVAP) found on liver sinusoidal endothelial cells (LSEC). Our pilot data confirms that PLVAP is markedly upregulated within the sinusoids as well as sites of fibrosis during CLD. We hypothesise that PLVAP alters permeability of LSEC and mediates lymphocyte recruitment from the systemic circulation in CLD. Key goals will be to study the expression and regulation of PLVAP in human liver tissue and primary human LSEC. Flow adhesion assays and permeability studies will be utilised to elucidate the function of PLVAP in LSEC. These studies may identify PLVAP as potential therapeutic target for CLD.