Fibrinogen induces endothelial cell permeability.
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 alpha(5)beta(1) 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.
Tyagi
Neetu
N
Department of Physiology and Biophysics, Health Sciences Center, A-1115, University of Louisville, Louisville, KY 40292, USA.
Roberts
Andrew M
AM
Dean
William L
WL
Tyagi
Suresh C
SC
Lominadze
David
D
D000199:Actins / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000209:etiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats
D000199:Actins; D000418:Albumins; D005419:Flavonoids; D019012:Integrin beta1; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one