Hyaluronic Acid Binding Protein 2 (synonym for factor VII-activating protease, FSAP) expression and activity are upregulated in the lungs of patients with acute respiratory distress syndrome, a disease with prominent vascular leakiness. The authors examined the role of HABP2 in vascular integrity using in vitro models of pulmonary EC barrier function and in vivo models of acute lung injury (ALI) with pulmonary vascular hyperpermeability.

 The findings indicate that HABP2, although primarily localized in the plasma, is upregulated in the lung endothelium with LPS-induced ALI and in cultured human pulmonary ECs. The enzymatic activity of HABP2 is differentially regulated by HA, with HMW-HA inhibiting HABP2 protease activity and LMW-HA binding to the PABD of HABP2 and stimulating activity. Activated HABP2 induces protease-activated receptor signaling in ECs, which leads to activation of the actin regulatory molecules RhoA and ROCK and endothelial barrier disruption. The barrier-disruptive role of HABP2 is further confirmed by vascular silencing of HABP2 expression, which attenuated the vascular leakiness observed in LPS- and ventilator-induced lung injury.

Title:
Hyaluronic Acid Binding Protein 2 Is a Novel Regulator of Vascular Integrity

Authors and Source:
Mambetsariev N et al. Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):483-490.