The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis
Open accessAbstract
Septic shock is characterized by increased vascular permeability and hypotension despite increased cardiac output. Numerous vasoactive cytokines are upregulated during sepsis, including angiopoietin 2 (ANG2), which increases vascular permeability. Here we report that mice engineered to inducibly overexpress ANG2 in the endothelium developed sepsis-like hemodynamic alterations, including systemic hypotension, increased cardiac output, and dilatory cardiomyopathy. Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to develop hemodynamic alterations. Interestingly, the hemodynamic alterations associated with endothelial-specific overexpression of ANG2 and the loss of capillary-associated pericytes were reversed by intravenous injections of adeno-associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice, which rapidly developed hypotension, acute pericyte loss, and increased vascular permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to 61%. These data indicate that ANG2-mediated microvascular disintegration contributes to septic shock and that inhibition of the ANG2/TIE2 interaction during sepsis is a potential therapeutic target.
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Cites
Pericytes regulate the blood–brain barrier
Armulik, A., Genové, G., Mäe, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., He, L., Norlin, J., Lindblom, P., Strittmatter, K., et al. (2010) · Nature · doi:10.1038/nature09522 · Cited by 2,843
Pericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises
Armulik, A., Genové, G., & Betsholtz, C. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.07.001 · Cited by 2,653
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
Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling
Felcht, M., Luck, R., Schering, A., Seidel, P., Srivastava, K., Hu, J., Bartol, A., Kienast, Y., Vettel, C., Loos, E. K., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58832 · Cited by 479
Self-citationDe Domenico, I., Zhang, T. Y., Koening, C. L., Branch, R. W., London, N., Lo, E., Daynes, R. A., Kushner, J. P., Li, D., Ward, D. M., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42011 · Cited by 197
Thomas, M., Felcht, M., Kruse, K., Kretschmer, S., Deppermann, C., Biesdorf, A., Rohr, K., Benest, A. V., Fiedler, U., & Augustin, H. G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.097543 · Cited by 101
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Cited by
Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges
Fukumura, D., Kloepper, J., Amoozgar, Z., Duda, D. G., & Jain, R. K. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.29 · Cited by 2,027
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
Plastic roles of pericytes in the blood–retinal barrier
Park, D. Y., Lee, J., Kim, J., Kim, K., Hong, S., Han, S., Kubota, Y., Augustin, H. G., Ding, L., Kim, J. W., et al. (2017) · Nature Communications · doi:10.1038/ncomms15296 · Cited by 322
Self-citationThe effects of sepsis on endothelium and clinical implications
Dolmatova, E. V., Wang, K., Mandavilli, R., & Griendling, K. K. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa070 · Cited by 317
Er, E. E., Valiente, M., Ganesh, K., Zou, Y., Agrawal, S., Hu, J., Griscom, B., Rosenblum, M., Boire, A., Brogi, E., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0138-8 · Cited by 292
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Metadata
- Authors
- Ziegler, T., Horstkotte, J., Schwab, C., Pfetsch, V., Weinmann, K., Dietzel, S., Rohwedder, I., Hinkel, R., Gross, L., Lee, S., Hu, J., Soehnlein, O., Franz, W. M., Sperandio, M., Pohl, U., Thomas, M., Weber, C., Augustin, H. G., Fässler, R., Deutsch, U., & Kupatt, C.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-07-01
- Volume
- 123
- Issue
- 8
- Pages
- 3436-3445
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2005564031
- Cited by
- 191
- References
- 6
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ziegler, T., Horstkotte, J., Schwab, C., Pfetsch, V., Weinmann, K., Dietzel, S., Rohwedder, I., Hinkel, R., Gross, L., Lee, S., Hu, J., Soehnlein, O., Franz, W. M., Sperandio, M., Pohl, U., Thomas, M., Weber, C., Augustin, H. G., Fässler, R., . . . Kupatt, C. (2013). Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis. Journal of Clinical Investigation. https://doi.org/10.1172/jci66549
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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