The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis*
Open accessAbstract
OBJECTIVE: : In sepsis, quiescent blood vessels become leaky and inflamed by mechanisms that are incompletely understood. We hypothesized that angiopoietin-2, a partial antagonist of the endothelium-stabilizing receptor Tie-2 secreted by endothelium, contributes to adverse outcomes in this disease. DESIGN: : Laboratory and animal research. SETTINGS: : Research laboratories and Emergency Department of Beth Israel Deaconess Medical Center, Boston, MA. SUBJECTS: : Angiopoietin-2 heterozygous mice, emergency department patients. MEASUREMENTS AND MAIN RESULTS: : Mice with one functional angiopoietin-2 allele developed milder kidney and lung injury, less tissue inflammation, and less vascular leakage compared to wild-type counterparts. Heterozygotes experienced >40% absolute survival advantage following two different models of sepsis (p = .004 and .018). In human subjects presenting to our emergency department with suspected infection (n = 270 combined), circulating angiopoietin-2 was markedly elevated within the first hour of clinical care. First-hour angiopoietin-2 concentrations were proportional to current disease severity (p < .0001), rose further over time in eventual nonsurvivors (p < .0001), and predicted the future occurrence of shock (p < .0001) or death (p < .0001) in the original cohort and an independent validation group. Finally, septic human serum disrupted the barrier function of microvascular endothelial cells, an effect fully neutralized by an angiopoietin-2 monoclonal antibody. CONCLUSIONS: : We conclude that angiopoietin-2 induction precedes and contributes to the adverse outcomes in sepsis, opening a new avenue for therapeutic investigation.
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DeLong, E. R., DeLong, D. M., & Clarke-Pearson, D. L. (1988) · Biometrics · doi:10.2307/2531595 · Cited by 22,649
Vincent, J. L., Moreno, R., Takala, J., Willatts, S., De Mendonça, A., Bruining, H., Reinhart, C. K., Suter, P. M., & Thijs, L. G. (1996) · Intensive Care Medicine · doi:10.1007/bf01709751 · Cited by 11,674
Early goal-directed therapy in the treatment of severe sepsis and septic shock
Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., & Tomlanovich, M. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010307 · Cited by 10,743
The epidemiology of sepsis in the United States from 1979 through 2000
Martin, G. S., Mannino, D. M., Eaton, S., & Moss, M. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022139 · Cited by 5,841
Fiedler, U., Reiss, Y., Scharpfenecker, M., Grunow, V., Koidl, S., Thurston, G., Gale, N. W., Witzenrath, M., Rosseau, S., Suttorp, N., et al. (2006) · Nature Medicine · doi:10.1038/nm1351 · Cited by 933
Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in Humans
Parikh, S. M., Mammoto, T., Schultz, A., Yuan, H.-T., Christiani, D., Karumanchi, S. A., & Sukhatme, V. P. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030046 · Cited by 527
Self-citationBroken Barriers: A New Take on Sepsis Pathogenesis
Goldenberg, N. M., Steinberg, B. E., Slutsky, A. S., & Lee, W. L. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002011 · Cited by 324
Cell-based Angiopoietin-1 Gene Therapy for Acute Lung Injury
McCarter, S. D., Mei, S. H. J., Lai, P. F. H., Zhang, Q. W., Parker, C. H., Suen, R. S., Hood, R. D., Zhao, Y. D., Deng, Y., Han, R. N. N., et al. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200609-1370oc · Cited by 154
Cited by
Therapeutic targeting of the angiopoietin–TIE pathway
Saharinen, P., Eklund, L., & Alitalo, K. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.278 · Cited by 620
Endothelial barrier dysfunction in septic shock
Opal, S. M., & van der Poll, T. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12331 · Cited by 353
Tie1 controls angiopoietin function in vascular remodeling and inflammation
Korhonen, E. A., Lampinen, A., Giri, H., Anisimov, A., Kim, M., Allen, B., Fang, S., D’Amico, G., Sipilä, T. J., Lohela, M., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84923 · Cited by 283
Angiopoietin‐2: a multifaceted cytokine that functions in both angiogenesis and inflammation
Scholz, A., Plate, K. H., & Reiss, Y. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12726 · Cited by 248
Amelioration of sepsis by TIE2 activation–induced vascular protection
Han, S., Lee, S.-J., Kim, K. E., Lee, H. S., Oh, N., Park, I., Ko, E., Oh, S. J., Lee, Y.-S., Kim, D., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad9260 · Cited by 203
Metadata
- Authors
- David, S., Mukherjee, A., Ghosh, C. C., Yano, M., Khankin, E. V., Wenger, J. B., Karumanchi, S. A., Shapiro, N. I., & Parikh, S. M.
- Venue
- Critical Care Medicine
- Published
- 2012-11
- Volume
- 40
- Issue
- 11
- Pages
- 3034-3041
- ISSN
- 0090-3493 (ISSN-L)
- OpenAlex
- W1993980694
- Cited by
- 193
- References
- 8
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Open access
- green
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- David, S., Mukherjee, A., Ghosh, C. C., Yano, M., Khankin, E. V., Wenger, J. B., Karumanchi, S. A., Shapiro, N. I., & Parikh, S. M. (2012). Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis*. Critical Care Medicine. https://doi.org/10.1097/ccm.0b013e31825fdc31
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