Thromb Haemost 2004; 92(01): 140-150
DOI: 10.1160/TH03-07-0491
Endothelium and Vascular Development
Schattauer GmbH

P-cresol, a uremic retention solute, alters the endothelial barrier function in vitro

Claire Cerini
1   INSERM EMI0019, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France
,
Laetitia Dou
1   INSERM EMI0019, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France
,
Francine Anfosso
1   INSERM EMI0019, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France
,
Florence Sabatier
1   INSERM EMI0019, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France
,
Valérie Moal
2   Service de Néphrologie, Hôpital de la Conception, Marseille, France
,
Griet Glorieux
3   Nephrology Department, University Hospital, Ghent, Belgium
,
Rita De Smet
3   Nephrology Department, University Hospital, Ghent, Belgium
,
Raymond Vanholder
3   Nephrology Department, University Hospital, Ghent, Belgium
,
Françoise Dignat-George
1   INSERM EMI0019, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France
,
José Sampol
1   INSERM EMI0019, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France
,
Yvon Berland
2   Service de Néphrologie, Hôpital de la Conception, Marseille, France
,
Philippe Brunet
1   INSERM EMI0019, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France
2   Service de Néphrologie, Hôpital de la Conception, Marseille, France
› Author Affiliations

Financial support: This work was financed by the Institut National de la Santé et de la Recherche Médicale (INSERM)
Further Information

Publication History

Received 29 July 2003

Accepted after resubmission 29 March 2004

Publication Date:
29 November 2017 (online)

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Summary

Patients with chronic renal failure (CRF) exhibit endothelial dysfunction, which may involve uremic retention solutes that accumulate in blood and tissues. In this study, we investigated the in vitro effect of the uremic retention solute p-cresol on the barrier function of endothelial cells (HUVEC). P-cresol was tested at concentrations found in CRF patients, and since p-cresol is protein-bound, experiments were performed with and without physiological concentration of human albumin (4 g/dl).With albumin, we showed that p-cresol caused a strong increase in endothelial permeability after a 24-hour exposure. Concomitant with this increase in endothelial permeability, p-cresol induced a reorganization of the actin cytoskeleton and an alteration of adherens junctions. These molecular events were demonstrated by the decreased staining of cortical actin, associated with the formation of stress fibers across the cell, and by the decreased staining of junctional VE-cadherin. This decrease in junctional VE-cadherin staining was not associated with a reduction of membrane expression. Without albumin, the effects of p-cresol were more pronounced. The specific Rho kinase inhibitor, Y-27632, inhibited the effects of p-cresol, indicating that p-cresol mediates the increase in endothelial permeability in a Rho kinase-dependent way. In conclusion, these results show that p-cresol causes a severe dysfunction of endothelial barrier function in vitro and suggest this uremic retention solute may participate in the endothelium dysfunction observed in CRF patients.