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Fibrinogen induces endothelial cell permeability

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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.

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Acknowledgements

This project was supported in part by the AHA, 0235317N to DL and GIA to WLD; NIH, HL-80394 to DL, HL-71010, HL-74185, HL-88012 and NS-51568 to SCT; ALA, Kentucky Affiliate to AMR.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Health Sciences Center, A-1115, University of Louisville, Louisville, KY, 40292, USA

    Neetu Tyagi, Andrew M. Roberts, Suresh C. Tyagi & David Lominadze

  2. Department of Biochemistry and Molecular Biology, Health Sciences Center, University of Louisville, Louisville, KY, 40292, USA

    William L. Dean

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  1. Neetu Tyagi
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  2. Andrew M. Roberts
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  3. William L. Dean
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  4. Suresh C. Tyagi
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  5. David Lominadze
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Correspondence to David Lominadze.

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Tyagi, N., Roberts, A.M., Dean, W.L. et al. Fibrinogen induces endothelial cell permeability. Mol Cell Biochem 307, 13–22 (2008). https://doi.org/10.1007/s11010-007-9579-2

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