Article

Molecular and Cellular Biochemistry

, Volume 307, Issue 1, pp 13-22

First online:

Fibrinogen induces endothelial cell permeability

  • Neetu TyagiAffiliated withDepartment of Physiology and Biophysics, Health Sciences Center, A-1115, University of Louisville
  • , Andrew M. RobertsAffiliated withDepartment of Physiology and Biophysics, Health Sciences Center, A-1115, University of Louisville
  • , William L. DeanAffiliated withDepartment of Biochemistry and Molecular Biology, Health Sciences Center, University of Louisville
  • , Suresh C. TyagiAffiliated withDepartment of Physiology and Biophysics, Health Sciences Center, A-1115, University of Louisville
  • , David LominadzeAffiliated withDepartment of Physiology and Biophysics, Health Sciences Center, A-1115, University of Louisville Email author 

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Abstract

Many cardiovascular and cerebrovascular disorders are accompanied by an increased blood content of fibrinogen (Fg), a high molecular weight plasma adhesion protein. Fg is a biomarker of inflammation and its degradation products have been associated with microvascular leakage. We tested the hypothesis that at pathologically high levels, Fg increases endothelial cell (EC) permeability through extracellular signal regulated kinase (ERK) signaling and by inducing F-actin formation. In cultured ECs, Fg binding to intercellular adhesion molecule-1 and to α5β1 integrin, caused phosphorylation of ERK. Subsequently, F-actin formation increased and coincided with formation of gaps between ECs, which corresponded with increased permeability of ECs to albumin. Our data suggest that formation of F-actin and gaps may be the mechanism for increased albumin leakage through the EC monolayer. The present study indicates that elevated un-degraded Fg may be a factor causing microvascular permeability that typically accompanies cardiovascular and cerebrovascular disorders.

Keywords

Albumin α5β1 integrin ERK F-actin Intercellular adhesion molecule-1