| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Cardiovascular Biology Research Program,* Oklahoma Medical Research Foundation, Oklahoma City; and the Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Endothelium plays a critical role in the pathobiology of sepsis by integrating systemic host responses and local rheological stimuli. We studied the differential expression and activation of tissue factor (TF)-dependent coagulation on linear versus branched arterial segments in a baboon sepsis model. Animals were injected intravenously with lethal doses of Escherichia coli or saline and sacrificed after 2 to 8 hours. Whole-mount arterial segments were stained for TF, TF-pathway inhibitor (TFPI), factor VII (FVII), and markers for endothelial cells (ECs), leukocytes, and platelets, followed by confocal microscopy and image analysis. In septic animals, TF localized preferentially at branches, EC surface, leukocytes, and platelet aggregates and accumulated in large amounts in the subendothelial space. FVII strongly co-localized with TF on ECs and leukocytes but less so with subendothelial TF. TFPI co-localized with TF and FVII on endothelium and leukocytes but not in the subendothelial space. Focal TF increases correlated with fibrin deposition and increased endothelial permeability to plasma proteins. Biochemical analysis confirmed that aortas of septic baboons expressed more TF mRNA and protein than controls. Branched segments contained higher TF protein levels and coagulant activity than equivalent linear areas. These data suggest that site-dependent endothelial heterogeneity and rheological factors contribute to focal procoa-gulant responses to E. coli.
This article has been cited by other articles:
 |
|
 |
|
  A. Shibamiya, K. Hersemeyer, T. Schmidt Woll, D. Sedding, J.-M. Daniel, S. Bauer, T. Koyama, K. T. Preissner, and S. M. Kanse A key role for Toll-like receptor-3 in disrupting the hemostasis balance on endothelial cells Blood, January 15, 2009; 113(3): 714 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Furie and B. C. Furie Mechanisms of Thrombus Formation N. Engl. J. Med., August 28, 2008; 359(9): 938 - 949. [Full Text] [PDF]
|
|
|
|
 |
|
 G. T. Roberts, H. Ghebeh, M. A. Chishti, F. Al-Mohanna, R. El-Sayed, F. Al-Mohanna, and A. Bouchama Microvascular Injury, Thrombosis, Inflammation, and Apoptosis in the Pathogenesis of Heatstroke: A Study in Baboon Model Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1130 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schouten, W. J. Wiersinga, M. Levi, and T. van der Poll Inflammation, endothelium, and coagulation in sepsis J. Leukoc. Biol., March 1, 2008; 83(3): 536 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tang, L. Ivanciu, N. Popescu, G. Peer, E. Hack, C. Lupu, F. B. Taylor Jr, and F. Lupu Sepsis-Induced Coagulation in the Baboon Lung Is Associated with Decreased Tissue Factor Pathway Inhibitor Am. J. Pathol., September 1, 2007; 171(3): 1066 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mackman, R. E. Tilley, and N. S. Key Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1687 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Aird Phenotypic Heterogeneity of the Endothelium: I. Structure, Function, and Mechanisms Circ. Res., February 2, 2007; 100(2): 158 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Aird Phenotypic Heterogeneity of the Endothelium: II. Representative Vascular Beds Circ. Res., February 2, 2007; 100(2): 174 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ivanciu, R. D. Gerard, H. Tang, F. Lupu, and C. Lupu Adenovirus-Mediated Expression of Tissue Factor Pathway Inhibitor-2 Inhibits Endothelial Cell Migration and Angiogenesis Arterioscler. Thromb. Vasc. Biol., February 1, 2007; 27(2): 310 - 316. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
