SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on January 23, 2003; DOI 10.1182/blood-2002-06-1887. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-06-1887v1 101/10/3765    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Aird, W. C. Search for Related Content PubMed PubMed Citation Articles by Aird, W. C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Phagocytes Apoptosis Cell Adhesion and Motility Review Articles Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2003, Vol. 101, No. 10, pp. 3765-3777 REVIEW ARTICLE The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome William C. Aird From the Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. Severe sepsis, defined as sepsis with acute organ dysfunction, is associated with high morbidity and mortality rates. The development of novel therapies for sepsis is critically dependent on an understanding of the basic mechanisms of the disease. The pathophysiology of severe sepsis involves a highly complex, integrated response that includes the activation of a number of cell types, inflammatory mediators, and the hemostatic system. Central to this process is an alteration of endothelial cell function. The goals of this article are to (1) provide an overview of sepsis and its complications, (2) discuss the role of the endothelium in orchestrating the host response in sepsis, and (3) emphasize the potential value of the endothelium as a target for sepsis therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Ye, J. Ding, X. Zhou, G. Chen, and S. F. Liu Divergent roles of endothelial NF-{kappa}B in multiple organ injury and bacterial clearance in mouse models of sepsis J. Exp. Med., June 9, 2008; 205(6): 1303 - 1315. [Abstract] [Full Text] [PDF] W.S. Bartynski Posterior Reversible Encephalopathy Syndrome, Part 2: Controversies Surrounding Pathophysiology of Vasogenic Edema AJNR Am. J. Neuroradiol., June 1, 2008; 29(6): 1043 - 1049. [Abstract] [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. Mofarrahi, T. Nouh, S. Qureshi, L. Guillot, D. Mayaki, and S. N. A. Hussain Regulation of angiopoietin expression by bacterial lipopolysaccharide Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L955 - L963. [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] A. P. Wheeler Recent Developments in the Diagnosis and Management of Severe Sepsis Chest, December 1, 2007; 132(6): 1967 - 1976. [Abstract] [Full Text] [PDF] D. Borgel, C. Bornstain, P. H. Reitsma, N. Lerolle, S. Gandrille, F. Dali-Ali, C. T. Esmon, J.-Y. Fagon, M. Aiach, and J.-L. Diehl A Comparative Study of the Protein C Pathway in Septic and Nonseptic Patients with Organ Failure Am. J. Respir. Crit. Care Med., November 1, 2007; 176(9): 878 - 885. [Abstract] [Full Text] [PDF] D. Liu, F. Lu, G. Qin, S. M. Fernandes, J. Li, and A. E. Davis III C1 Inhibitor-Mediated Protection from Sepsis J. Immunol., September 15, 2007; 179(6): 3966 - 3972. [Abstract] [Full Text] [PDF] M. Nguyen, A. J. Pace, and B. H. Koller Mice lacking NKCC1 are protected from development of bacteremia and hypothermic sepsis secondary to bacterial pneumonia J. Exp. Med., June 11, 2007; 204(6): 1383 - 1393. [Abstract] [Full Text] [PDF] W.-J. Zhang, H. Wei, T. Hagen, and B. Frei {alpha}-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway PNAS, March 6, 2007; 104(10): 4077 - 4082. [Abstract] [Full Text] [PDF] F. Fazal, M. Minhajuddin, K. M. Bijli, J. L. McGrath, and A. Rahman Evidence for Actin Cytoskeleton-dependent and -independent Pathways for RelA/p65 Nuclear Translocation in Endothelial Cells J. Biol. Chem., February 9, 2007; 282(6): 3940 - 3950. [Abstract] [Full Text] [PDF] K. Inoue, M. Kobayashi, K. Yano, M. Miura, A. Izumi, C. Mataki, T. Doi, T. Hamakubo, P. C. Reid, D. A. Hume, et al. Histone Deacetylase Inhibitor Reduces Monocyte Adhesion to Endothelium Through the Suppression of Vascular Cell Adhesion Molecule-1 Expression Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2652 - 2659. [Abstract] [Full Text] [PDF] W.S. Bartynski, J.F. Boardman, Z.R. Zeigler, R.K. Shadduck, and J. Lister Posterior Reversible Encephalopathy Syndrome in Infection, Sepsis, and Shock AJNR Am. J. Neuroradiol., November 1, 2006; 27(10): 2179 - 2190. [Abstract] [Full Text] [PDF] V. Vachharajani and S. Vital Obesity and sepsis. J Intensive Care Med, September 1, 2006; 21(5): 287 - 295. [Abstract] [PDF] K. Yano, P. C. Liaw, J. M. Mullington, S.-C. Shih, H. Okada, N. Bodyak, P. M. Kang, L. Toltl, B. Belikoff, J. Buras, et al. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality J. Exp. Med., June 12, 2006; 203(6): 1447 - 1458. [Abstract] [Full Text] [PDF] E. Camerer, I. Cornelissen, H. Kataoka, D. N. Duong, Y.-W. Zheng, and S. R. Coughlin Roles of protease-activated receptors in a mouse model of endotoxemia Blood, May 15, 2006; 107(10): 3912 - 3921. [Abstract] [Full Text] [PDF] R. E. Rumbaut, R. V. Bellera, J. K. Randhawa, C. N. Shrimpton, S. K. Dasgupta, J.-F. Dong, and A. R. Burns Endotoxin enhances microvascular thrombosis in mouse cremaster venules via a TLR4-dependent, neutrophil-independent mechanism Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1671 - H1679. [Abstract] [Full Text] [PDF] A. Tuin, A. Huizinga-Van der Vlag, A.-M. M. A. van Loenen-Weemaes, D. K. F. Meijer, and K. Poelstra On the role and fate of LPS-dephosphorylating activity in the rat liver Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G377 - G385. [Abstract] [Full Text] [PDF] E. P. Rivers, L. McIntyre, D. C. Morro, and K. K. Rivers Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity Can. Med. Assoc. J., October 25, 2005; 173(9): 1054 - 1065. [Abstract] [Full Text] [PDF] C. Lupu, A. D. Westmuckett, G. Peer, L. Ivanciu, H. Zhu, F. B. Taylor Jr., and F. Lupu Tissue Factor-Dependent Coagulation Is Preferentially Up-Regulated within Arterial Branching Areas in a Baboon Model of Escherichia coli Sepsis Am. J. Pathol., October 1, 2005; 167(4): 1161 - 1172. [Abstract] [Full Text] [PDF] M. Eto, A. Kouroedov, F. Cosentino, and T. F. Luscher Glycogen Synthase Kinase-3 Mediates Endothelial Cell Activation by Tumor Necrosis Factor-{alpha} Circulation, August 30, 2005; 112(9): 1316 - 1322. [Abstract] [Full Text] [PDF] S.-Q. Wu and W. C. Aird Thrombin, TNF-{alpha}, and LPS exert overlapping but nonidentical effects on gene expression in endothelial cells and vascular smooth muscle cells Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H873 - H885. [Abstract] [Full Text] [PDF] M. Minhajuddin, F. Fazal, K. M. Bijli, Md. R. Amin, and A. Rahman Inhibition of Mammalian Target of Rapamycin Potentiates Thrombin-Induced Intercellular Adhesion Molecule-1 Expression by Accelerating and Stabilizing NF-{kappa}B Activation in Endothelial Cells J. Immunol., May 1, 2005; 174(9): 5823 - 5829. [Abstract] [Full Text] [PDF] J. Seybold, D. Thomas, M. Witzenrath, S. Boral, A. C. Hocke, A. Burger, A. Hatzelmann, H. Tenor, C. Schudt, M. Krull, et al. Tumor necrosis factor-{alpha}-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability Blood, May 1, 2005; 105(9): 3569 - 3576. [Abstract] [Full Text] [PDF] S. Lacroix-Desmazes, J. Bayry, S. V. Kaveri, D. Hayon-Sonsino, N. Thorenoor, J. Charpentier, C.-E. Luyt, J.-P. Mira, V. Nagaraja, M. D. Kazatchkine, et al. From the Cover: High levels of catalytic antibodies correlate with favorable outcome in sepsis PNAS, March 15, 2005; 102(11): 4109 - 4113. [Abstract] [Full Text] [PDF] D. Liu, D. Zhang, J. Scafidi, X. Wu, C. C. Cramer, and A. E. Davis III C1 inhibitor prevents Gram-negative bacterial lipopolysaccharide-induced vascular permeability Blood, March 15, 2005; 105(6): 2350 - 2355. [Abstract] [Full Text] [PDF] A. Nooteboom, C. J. van der Linden, and T. Hendriks Whole blood-mediated endothelial permeability and adhesion molecule expression: a model study into the effects of bacteria and antibiotics J. Antimicrob. Chemother., February 1, 2005; 55(2): 150 - 156. [Abstract] [Full Text] [PDF] M-H Gaugler A unifying system: does the vascular endothelium have a role to play in multi-organ failure following radiation exposure? Br. J. Radiol., January 1, 2005; Supplement_27(1): 100 - 105. [Abstract] [Full Text] [PDF] F. Bossi, F. Fischetti, V. Pellis, R. Bulla, E. Ferrero, T. E. Mollnes, D. Regoli, and F. Tedesco Platelet-Activating Factor and Kinin-Dependent Vascular Leakage as a Novel Functional Activity of the Soluble Terminal Complement Complex J. Immunol., December 1, 2004; 173(11): 6921 - 6927. [Abstract] [Full Text] [PDF] K. N. Anwar, F. Fazal, A. B. Malik, and A. Rahman RhoA/Rho-Associated Kinase Pathway Selectively Regulates Thrombin-Induced Intercellular Adhesion Molecule-1 Expression in Endothelial Cells via Activation of I{kappa}B Kinase {beta} and Phosphorylation of RelA/p65 J. Immunol., December 1, 2004; 173(11): 6965 - 6972. [Abstract] [Full Text] [PDF] L. B. Ware, M. D. Eisner, B. T. Thompson, P. E. Parsons, and M. A. Matthay Significance of Von Willebrand Factor in Septic and Nonseptic Patients with Acute Lung Injury Am. J. Respir. Crit. Care Med., October 1, 2004; 170(7): 766 - 772. [Abstract] [Full Text] [PDF] G. Schabbauer, M. Tencati, B. Pedersen, R. Pawlinski, and N. Mackman PI3K-Akt Pathway Suppresses Coagulation and Inflammation in Endotoxemic Mice Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1963 - 1969. [Abstract] [Full Text] [PDF] E. Andreakos, S. M. Sacre, C. Smith, A. Lundberg, S. Kiriakidis, T. Stonehouse, C. Monaco, M. Feldmann, and B. M. Foxwell Distinct pathways of LPS-induced NF-{kappa}B activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP Blood, March 15, 2004; 103(6): 2229 - 2237. [Abstract] [Full Text] [PDF] A. Carrillo, Y. Monreal, P. Ramirez, L. Marin, P. Parrilla, F. J. Oliver, and J. Yelamos Transcription regulation of TNF-{alpha}-early response genes by poly(ADP-ribose) polymerase-1 in murine heart endothelial cells Nucleic Acids Res., February 3, 2004; 32(2): 757 - 766. [Abstract] [Full Text] [PDF] Z. Shariat-Madar and A. H. Schmaier Review: The plasma kallikrein/kinin and renin angiotensin systems in blood pressure regulation in sepsis Innate Immunity, February 1, 2004; 10(1): 3 - 13. [Abstract] [PDF] T. Minami, A. Sugiyama, S.-Q. Wu, R. Abid, T. Kodama, and W. C. Aird Thrombin and Phenotypic Modulation of the Endothelium Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 41 - 53. [Abstract] [Full Text] [PDF] B. A. Kerlin, S. B. Yan, B. H. Isermann, J. T. Brandt, R. Sood, B. R. Basson, D. E. Joyce, H. Weiler, and J.-F. Dhainaut Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia Blood, November 1, 2003; 102(9): 3085 - 3092. [Abstract] [Full Text] [PDF] C. H. Toh and M. Dennis Disseminated intravascular coagulation: old disease, new hope BMJ, October 25, 2003; 327(7421): 974 - 977. [Full Text] [PDF] D. C. Angus and M. A. Crowther Unraveling Severe Sepsis: Why Did OPTIMIST Fail and What's Next? JAMA, July 9, 2003; 290(2): 256 - 258. [Full Text] [PDF] T. E. Warkentin, W. C. Aird, and J. H. Rand Platelet-Endothelial Interactions: Sepsis, HIT, and Antiphospholipid Syndrome Hematology, January 1, 2003; 2003(1): 497 - 519. [Abstract] [Full Text] [PDF]