Role of PV1 in Lung Vascular Barrier Regulation

Plasmalemmal Vesicle Associated Protein (PV1) is a glycoprotein that forms spoke-like structures (called diaphragms) found at the neck region of endothelial caveolae and the openings of fenestrated endothelium. Previous reports indicate that PV1 contributes to endothelial barrier integrity in fenestrated endothelium, restricting passive diffusion of fluid and protein into abdominal organs. Interestingly, PV1 is highly expressed in the lung, which lacks fenestrations and sinusoids. Yet, the role of PV1 in lung endothelial permeability and its contributions to caveolae-mediated transport remain unclear. In this study, we observed that postnatal loss of PV1 in adult mice resulted in red blood cell extravasation into lung tissue evidenced by appearance of petechiae on the pleural surface. We also observed an increase in lung vessel wall permeability following PV1 deletion, determined by an increase in fluid filtration and albumin transport. These findings were associated with a loss of plasma protein and blood pressure in mice. We used morphometric analysis to determine that loss of PV1 increased caveolar size and increased filling of luminal vesicles with albumin. Moreover, a greater number of endocytic vesicles and albumin particles were found in PV1 deficient endothelium. Our findings suggest that PV1 is an important regulator of lung vascular integrity and caveolae-mediated transport in capillary endothelium. Interestingly, we found that PV1 expression (mRNA) and protein are both reduced in lung endothelial cells following acute lung injury in mice. New lines of investigation are currently exploring the contribution of PV1 toward edema formation, inflammation, protein permeability, and mortality in mice following ALI.