Feng Wu, PhD

University of Western Ontario, PhD, Phyiology.

Vascular leakage is involved in the pathogenesis of lung permeability and tumor metastasis. Syndecan-1 is the protein backbone of glycocalyx lining the vascular endothelium and maintaining the endothelial integrity. We found for the first time that fibrinogen, the major component of plasma, binds with syndecan-1 to exert the protective effects on the lung endothelial integrity in mice after trauma/bacterial pneumonia. Fibrinogen binding to heparan sulfate on syndecan-1/glycocalyx forms a gel-like layer that lines the endothelium and maintains vascular barrier integrity. This gel-like layer shields the cleavage sites on syndecan-1/glycocalyx by MMP9, which otherwise cleaves syndecan-1/glycocalyx to cause lung vascular leakage. It is known that fibrinogen is oxidized in human trauma/pneumonia patients. Our study suggests that maintaining fibrinogen in reduced state and/or inhibiting MMP9 activity could provide a therapy for the lung injury in trauma/pneumonia patients. Since the ischemia after trauma/hemorrhage resembles the hypoxia microenvironment promoting tumor growth, maintaining fibrinogen in reduced state and/or inhibiting MMP9 activity could also be used to treating tumor metastasis through stabilizing the endothelial integrity.

Septic shock, hemorrhage shock, acute lung injury, vascular leakage, endothelial barrier dysfunction, stress fibers, antioxidants, syndecan-1, fibrinogen, miR-19b,

Fibrinogen protects vascular integrity and prevents lung injury.

Wu et al. Fibrinogen inhibits metalloproteinase-9 activation and syndecan-1 cleavage to protect lung function in ApoE null mice after hemorrhagic shock. J Surg Res 2023; 288:208-214.

Anti-miR-19b oligos protect the lungs in mice after hemorrhage shock.

Wu et al. miR-19b targets pulmonary endothelial syndecan-1 following hemorrhagic shock. Sci Rep. 2020; 10:15811.

Vitamin C intravenous injection increases survival in polymicrobial sepsis.

Wu et al. Ascorbate protects against impaired arteriolar constriction in sepsis by inhibiting iNOS expression. Free Radic Biol Med. 2004; 37:1282-1289.