Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

Rho Kinase Inhibition in Severe Malaria: Thwarting Parasite-Induced Collateral Damage to Endothelia

Zacharie Taoufiq, Frederick Gay, Judith Balvanyos, Liliane Ciceron, Maurel Tefit, Philippe Lechat and Dominique Mazier
The Journal of Infectious Diseases
Vol. 197, No. 7 (Apr. 1, 2008), pp. 1062-1073
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/40253930
Page Count: 12
  • Download ($42.00)
  • Subscribe ($19.50)
  • Cite this Item
Rho Kinase Inhibition in Severe Malaria: Thwarting Parasite-Induced Collateral Damage to Endothelia
Preview not available

Abstract

Acute clinical manifestations of falciparum malaria, such as multiorgan failure and cerebral malaria, occur unpredictably and lead to coma and death within hours if left untreated. Despite the emergency administration of effective antimalarial drugs, 15%-20% of patients die. Other therapeutic approaches are therefore urgently needed. There is increasing evidence that endothelial changes play a key role in the pathogenesis of severe malaria. We therefore used coculture models to study interactions between infected erythrocytes and endothelium. We found that adhesion of Plasmodium falciparum to endothelial cells in vitro activated the Rho kinase signaling pathway, which is strongly involved in various vascular diseases. When added concomitantly with parasites, the Rho kinase inhibitor fasudil (HA-1077), a drug already in clinical use, decreased both NF-KB activation and endothelial cell apoptosis. Fasudil also helped to restore endothelial barrier integrity after P. falciparum adhesion. Rho kinase inhibition thus appears to be a promising adjunctive therapeutic approach to the management of severe human malaria.

Page Thumbnails

  • Thumbnail: Page 
1062
    1062
  • Thumbnail: Page 
1063
    1063
  • Thumbnail: Page 
1064
    1064
  • Thumbnail: Page 
1065
    1065
  • Thumbnail: Page 
1066
    1066
  • Thumbnail: Page 
1067
    1067
  • Thumbnail: Page 
1068
    1068
  • Thumbnail: Page 
1069
    1069
  • Thumbnail: Page 
1070
    1070
  • Thumbnail: Page 
1071
    1071
  • Thumbnail: Page 
1072
    1072
  • Thumbnail: Page 
1073
    1073