Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in Humans
Open accessAbstract
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a devastating complication of numerous underlying conditions, most notably sepsis. Although pathologic vascular leak has been implicated in the pathogenesis of ARDS and sepsis-associated lung injury, the mechanisms promoting leak are incompletely understood. Angiopoietin-2 (Ang-2), a known antagonist of the endothelial Tie-2 receptor, was originally described as a naturally occurring disruptor of normal embryonic vascular development otherwise mediated by the Tie-2 agonist angiopoietin-1 (Ang-1). We hypothesized that Ang-2 contributes to endothelial barrier disruption in sepsis-associated lung injury, a condition involving the mature vasculature. METHODS AND FINDINGS: We describe complementary human, murine, and in vitro investigations that implicate Ang-2 as a mediator of this process. We show that circulating Ang-2 is significantly elevated in humans with sepsis who have impaired oxygenation. We then show that serum from these patients disrupts endothelial architecture. This effect of sepsis serum from humans correlates with measured Ang-2, abates with clinical improvement, and is reversed by Ang-1. Next, we found that endothelial barrier disruption can be provoked by Ang-2 alone. This signal is transduced through myosin light chain phosphorylation. Last, we show that excess systemic Ang-2 provokes pulmonary leak and congestion in otherwise healthy adult mice. CONCLUSIONS: Our results identify a critical role for Ang-2 in disrupting normal pulmonary endothelial function.
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ANG2, which is up-regulated in diseases associated with inflammation and vascular leakage, synergizes with multiple inflammatory agents, promoting endothelial permeability.
“Furthermore, the EC-derived growth factor angiopoietin-2 (ANG2, ANGPT2), which is up-regulated in diseases associated with inflammation and vascular leakage, synergizes with multiple inflammatory agents, promoting endothelial permeability (6, 7).”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [6]
The Results report elevated circulating Ang-2 in severe sepsis and show that Ang-2 alone increased endothelial-monolayer permeability by approximately 20%. The Discussion mentions inflammatory ligands and other causes of vascular leak, but does not establish that Ang-2 synergizes with multiple inflammatory agents; the disease finding is also specific to severe sepsis rather than diseases generally. The indexed passages provide section labels but no page numbers. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIncreased capillary leakage leading to hypovolemic shock and multiorgan failure is a key event in the pathobiology of several difficult-to-treat conditions, such as sepsis.
“Increased capillary leakage leading to hypovolemic shock and multiorgan failure is a key event in the pathobiology of several difficult-to-treat conditions, such as sepsis (2, 3, 6).”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [6]
The Introduction says capillary permeability is altered in sepsis, causing fluid to leave the vascular space, and notes that patients who develop shock and multi-organ dysfunction face the greatest risk of death. The Discussion identifies vascular leak as an early contributor to lung injury. Neither passage establishes that capillary leakage leads specifically to hypovolemic shock or multi-organ failure. (LLM, conf=0.85)
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Cites
(2000) · New England Journal of Medicine · doi:10.1056/nejm200005043421801 · Cited by 12,941 · see citing works
Angus, D. C., Linde-Zwirble, W. T., Lidicker, J., Clermont, G., Carcillo, J., & Pinsky, M. R. (2001) · Critical Care Medicine · doi:10.1097/00003246-200107000-00002 · Cited by 8,503 · see citing works
Rho GTPases and the Actin Cytoskeleton
Hall, A. (1998) · Science · doi:10.1126/science.279.5350.509 · Cited by 6,138 · see citing works
2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference
Levy, M. M., Fink, M. P., Marshall, J. C., Abraham, E. H., Angus, D. C., Cook, D., Cohen, J., Opal, S. M., Vincent, J., & Ramsay, G. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000050454.01978.3b · Cited by 5,976 · see citing works
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 · see citing works
The Acute Respiratory Distress Syndrome
Matthay, M. A. (1996) · New England Journal of Medicine · doi:10.1056/nejm199605303342209 · Cited by 4,924 · see citing works
The Acute Respiratory Distress Syndrome
Ware, L. B., & Matthay, M. A. (2000) · New England Journal of Medicine · doi:10.1056/nejm200005043421806 · Cited by 4,666 · see citing works
Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis
Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., et al. (1997) · Science · doi:10.1126/science.277.5322.55 · Cited by 3,570 · see citing works
A gene atlas of the mouse and human protein-encoding transcriptomes
Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400782101 · Cited by 3,475 · see citing works
Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase)
Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., et al. (1996) · Science · doi:10.1126/science.273.5272.245 · Cited by 2,889 · see citing works
Isolation of Angiopoietin-1, a Ligand for the TIE2 Receptor, by Secretion-Trap Expression Cloning
Davis, S., Aldrich, T. H., Jones, P. F., Acheson, A., Compton, D. L., Jain, V., Ryan, T. E., Bruno, J., Radziejewski, C., Maisonpierre, P. C., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81812-7 · Cited by 1,989 · see citing works
Leakage-Resistant Blood Vessels in Mice Transgenically Overexpressing Angiopoietin-1
Thurston, G., Suri, C., Smith, K., McClain, J., Sato, T. T., Yancopoulos, G. D., & McDonald, D. M. (1999) · Science · doi:10.1126/science.286.5449.2511 · Cited by 1,350 · see citing works
Angiopoietin-1 protects the adult vasculature against plasma leakage
Thurston, G., Rudge, J. S., Ioffe, E., Zhou, H., Ross, L. H., Croll, S. D., Glazer, N. L., Holash, J. A., McDonald, D. M., & Yancopoulos, G. D. (2000) · Nature Medicine · doi:10.1038/74725 · Cited by 1,284 · see citing works
Signaling Vascular Morphogenesis and Maintenance
Hanahan, D. (1997) · Science · doi:10.1126/science.277.5322.48 · Cited by 1,205 · see citing works
Inhibition of VEGF receptors causes lung cell apoptosis and emphysema
Kasahara, Y., Tuder, R. M., Taraseviciene‐Stewart, L., Cras, T. D. L., Abman, S. H., Hirth, P., Waltenberger, J. L., & Voelkel, N. F. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10259 · Cited by 1,110 · see citing works
Pathophysiological consequences of VEGF-induced vascular permeability
Weis, S. M., & Cheresh, D. A. (2005) · Nature · doi:10.1038/nature03987 · Cited by 911 · see citing works
Clinical Risks for Development of the Acute Respiratory Distress Syndrome
Hudson, L. D., MILBERG, J. A., Anardi, D. M., & Maunder, R. J. (1995) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.151.2.7842182 · Cited by 884 · see citing works
Fiedler, U., Scharpfenecker, M., Koidl, S., Hegen, A., Grunow, V., Schmidt, J. M., Kriz, W., Thurston, G., & Augustin, H. G. (2004) · Blood · doi:10.1182/blood-2003-10-3685 · Cited by 742 · see citing works
Improved Survival of Patients With Acute Respiratory Distress Syndrome (ARDS): 1983-1993
MILBERG, J. A. (1995) · JAMA · doi:10.1001/jama.1995.03520280052039 · Cited by 726 · see citing works
Bhatt, A., Pryhuber, G., Huyck, H. L., et al. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.10.2101140 · Cited by 602 · see citing works
Garcia, J. G. N., Davis, H. W., & Patterson, C. E. (1995) · Journal of Cellular Physiology · doi:10.1002/jcp.1041630311 · Cited by 550 · see citing works
Bernard, G. R., Artigas, A., Brigham, K. L., Carlet, J. M., Falke, K. J., Hudson, L. D., Lamy, M., Gall, J. R. L., Morris, A. H., & Spragg, R. G. (1994) · Journal of Critical Care · doi:10.1016/0883-9441(94)90033-7 · Cited by 430 · see citing works
Papapetropoulos, A., García‐Cardeña, G., Dengler, T. J., Maisonpierre, P. C., Yancopoulos, G. D., & Sessa, W. C. (1999) · PubMed · Cited by 418 · see citing works
Identification of a Putative Target for Rho as the Serine-Threonine Kinase Protein Kinase N
Amano, M., Mukai, H., Ono, Y., Chihara, K., Matsui, T., Hamajima, Y., Okawa, K., Iwamatsu, A., & Kaibuchi, K. (1996) · Science · doi:10.1126/science.271.5249.648 · Cited by 417 · see citing works
Tie2 Expression and Phosphorylation in Angiogenic and Quiescent Adult Tissues
Wong, A. L., Haroon, Z. A., Werner, S., Dewhirst, M. W., Greenberg, C. S., & Peters, K. G. (1997) · Circulation Research · doi:10.1161/01.res.81.4.567 · Cited by 417 · see citing works
Mandriota, S. J., & Pepper, M. S. (1998) · Circulation Research · doi:10.1161/01.res.83.8.852 · Cited by 382 · see citing works
Kim, I., Moon, S.-O., Park, S. K., Chae, S., & Koh, G. Y. (2001) · Circulation Research · doi:10.1161/hh1801.097034 · Cited by 368 · see citing works
Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase.
Ikebe, M., & Hartshorne, D. J. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39206-2 · Cited by 346 · see citing works
Brun‐Buisson, C., Doyon, F., & Carlet, J. M. (1996) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.154.3.8810595 · Cited by 340 · see citing works
Teichert-Kuliszewska, K. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00231-5 · Cited by 290 · see citing works
Involvement of myosin light-chain kinase in endothelial cell retraction.
Wysolmerski, R. B., & Lagunoff, D. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.1.16 · Cited by 247 · see citing works
Saharinen, P., Kerkelä, K., Ekman, N., Marron, M. B., Brindle, N. P. J., Lee, G. M., Augustin, H. G., Koh, G. Y., & Alitalo, K. K. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200411105 · Cited by 233 · see citing works
Endothelial gaps and permeability of venules in rat tracheas exposed to inflammatory stimuli
McDonald, D. M. (1994) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1994.266.1.l61 · Cited by 222 · see citing works
Angiopoietin-2 Causes Inflammation in Vivo by Promoting Vascular Leakage
Roviezzo, F., Tsigkos, S., Kotanidou, A. N., Bucci, M., Brancaleone, V., Cirino, G., & Papapetropoulos, A. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.086553 · Cited by 221 · see citing works
Endothelial Gaps as Sites for Plasma Leakage in Inflammation
McDonald, D. M., Thurston, G., & Bałuk, P. (1999) · Microcirculation · doi:10.1111/j.1549-8719.1999.tb00084.x · Cited by 218 · see citing works
Hypoxic Regulation of Angiopoietin-2 Expression in Endothelial Cells
Pichiule, P., Chavez, J. C., & LaManna, J. C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m305146200 · Cited by 209 · see citing works
Protective Role of Angiopoietin-1 in Endotoxic Shock
Witzenbichler, B., Westermann, D., Knueppel, S., Schultheiss, H., & Tschöpe, C. (2004) · Circulation · doi:10.1161/01.cir.0000151287.08202.8e · Cited by 199 · see citing works
Angiopoietin-1 Promotes Cardiac and Skeletal Myocyte Survival Through Integrins
Dallabrida, S. M., Ismail, N. S., Oberle, J., Himes, B. E., & Rupnick, M. A. (2005) · Circulation Research · doi:10.1161/01.res.0000158285.57191.60 · Cited by 192 · see citing works
PLASMA VASCULAR ENDOTHELIAL GROWTH FACTOR IN SEVERE SEPSIS
van der Flier, M., van Leeuwen, H. J., van Kessel, K. P. M., Kimpen, J. L. L., Hoepelman, A. I. M., & Geelen, S. P. M. (2004) · Shock · doi:10.1097/01.shk.0000150728.91155.41 · Cited by 185 · see citing works
Tumor necrosis factor and interleukin 1 alpha increase vascular endothelial permeability
Royall, J. A., Berkow, R. L., Beckman, J. S., et al. (1989) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1989.257.6.l399 · Cited by 183 · see citing works
Angiogenic Actions of Angiopoietin-1 Require Endothelium-Derived Nitric Oxide
Babaei, S., Teichert-Kuliszewska, K., Zhang, Q., Jones, N., Dumont, D., & Stewart, D. J. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64326-x · Cited by 182 · see citing works
Chong, A., Caine, G. J., Freestone, B., Blann, A. D., & Lip, G. Y. H. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.08.042 · Cited by 169 · see citing works
Wainwright, M. S., Rossi, J. L., Schavocky, J. P., Crawford, S. E., Steinhorn, D. M., Velentza, A. V., Zasadzki, M., Shirinsky, V. P., Jia, Y., Haiech, J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031595100 · Cited by 144 · see citing works
IL-1 and IFN-gamma increase vascular permeability.
Martin, S., Maruta, K., Burkart, V., Gillis, S. A., & Kolb, H. (1988) · PubMed Central · Cited by 136 · see citing works
Endothelial Gaps as Sites for Plasma Leakage in Inflammation
McDonald, D. M., Thurston, G., & Bałuk, P. (1999) · Microcirculation · doi:10.1080/713773924 · Cited by 130 · see citing works
Intracellular signalling involved in modulating human endothelial barrier function*
van Hinsbergh, V. W. M., & Amerongen, G. P. V. N. (2002) · Journal of Anatomy · doi:10.1046/j.1469-7580.2002.00060.x · Cited by 128 · see citing works
Iivanainen, E., Nelimarkka, L. O., Elenius, V., Heikkinen, S.-M., Junttila, T. T., Sihombing, L., Sundvall, M., Määttä, J. A., Laine, V. J. O., Ylä‐Herttuala, S., et al. (2003) · The FASEB Journal · doi:10.1096/fj.02-0939com · Cited by 125 · see citing works
Transvascular flux and tissue accrual of Evans blue: effects of endotoxin and histamine.
Green, T. P., Johnson, D. E., Marchessault, R. P., & Gatto, C. W. (1988) · PubMed · Cited by 116 · see citing works
Role of myosin light-chain phosphorylation in endothelial cell retraction
Sheldon, R. D., Moy, A. B., Lindsley, K. A., et al. (1993) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1993.265.6.l606 · Cited by 115 · see citing works
C1-inhibitor in patients with severe sepsis and septic shock: Beneficial effect on renal dysfunction
Caliezi, C., Zeerleder, S. S., Redondo, M., Regli, B., Rothen, H.-U., Zenklusen, R. M. Z., Rieben, R., Devay, J., Hack, C. E., Lämmle, B., et al. (2002) · Critical Care Medicine · doi:10.1097/00003246-200208000-00008 · Cited by 99 · see citing works
Verin, A. D., Patterson, C. E., Day, M.-C., et al. (1995) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1995.269.1.l99 · Cited by 98 · see citing works
Tinsley, J. H., de Lanerolle, P., Wilson, E., et al. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.279.4.c1285 · Cited by 87 · see citing works
Kamisoyama, H., Araki, Y., & Ikebe, M. (1994) · Biochemistry · doi:10.1021/bi00169a027 · Cited by 81 · see citing works
Calandrino, F. S., Anderson, D. J., Mintun, M. A., et al. (1988) · American Review of Respiratory Disease · doi:10.1164/ajrccm/138.2.421 · Cited by 76 · see citing works
Differential expression of Tie-2 receptors and angiopoietins in response to in vivo hypoxia in rats
Abdulmalek, K., Ashur, F., Ezer, N. N., Ye, F., Magder, S. A., & Hussain, S. N. A. (2001) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2001.281.3.l582 · Cited by 68 · see citing works
Myosin light chain phosphorylation and pulmonary endothelial cell hyperpermeability in burns
Tinsley, J. H., Teasdale, N. R., & Yuan, S. Y. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00341.2003 · Cited by 59 · see citing works
Wang, Y., Pampou, S., Fujikawa, K., & Varticovski, L. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10386 · Cited by 57 · see citing works
Rinkema, L. E., Bemis, K. G., & Fleisch, J. H. (1984) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21635-4 · Cited by 51 · see citing works
Gamma scintigraphic analysis of albumin flux in patients with acute respiratory distress syndrome.
Hj, S., Jl, T., BURKE, T. S., et al. (1984) · PubMed · Cited by 38 · see citing works
Sugerman, H. J., Strash, A. M., Hirsch, J. I., et al. (1981) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/00005373-198107000-00003 · Cited by 37 · see citing works
Nolan, A., Weiden, M. D., Thurston, G., & Gold, J. A. (2004) · Inflammation · doi:10.1007/s10753-004-6050-3 · Cited by 36 · see citing works
Groeneveld, A. B. J., & Raijmakers, P. G. H. M. (1998) · Critical Care Medicine · doi:10.1097/00003246-199804000-00016 · Cited by 26 · see citing works
Comparative scintigraphy in oleic acid pulmonary microvascular injury
Sugerman, H. J., Hirsch, J. I., TATUM, D. J. L., et al. (1982) · Critical Care Medicine · doi:10.1097/00003246-198201000-00008 · Cited by 17 · see citing works
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Sorted by citations
Every step of the way: integrins in cancer progression and metastasis
Hamidi, H., & Ivaska, J. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0038-z · Cited by 1,493 · see citing works
A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice
Huh, D., Leslie, D. C., Matthews, B. D., Fraser, J. P., Jurek, S., Hamilton, G. A., Thorneloe, K. S., McAlexander, M. A., & Ingber, D. E. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004249 · Cited by 993 · see citing works
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 · see citing works
Broken 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 · see citing works
Endothelial destabilization by angiopoietin-2 via integrin β1 activation
Hakanpaa, L., Sipila, T., Leppanen, V.-M., Gautam, P., Nurmi, H., Jacquemet, G., Eklund, L., Ivaska, J., Alitalo, K., & Saharinen, P. (2015) · Nature Communications · doi:10.1038/ncomms6962 · Cited by 287 · see citing works
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 · see citing works
The pulmonary pathology of COVID-19
Bösmüller, H., Matter, M., Fend, F., & Tzankov, A. (2021) · Virchows Archiv · doi:10.1007/s00428-021-03053-1 · Cited by 180 · see citing works
Angiopoietin-2 Is Critical for Cytokine-Induced Vascular Leakage
Benest, A. V., Kruse, K., Savant, S., Thomas, M., Laib, A. M., Loos, E. K., Fiedler, U., & Augustin, H. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070459 · Cited by 178 · see citing works
Targeting β1-integrin inhibits vascular leakage in endotoxemia
Hakanpaa, L., Kiss, E. A., Jacquemet, G., Miinalainen, I., Lerche, M., Guzmán, C., Mervaala, E., Eklund, L., Ivaska, J., & Saharinen, P. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1722317115 · Cited by 95 · see citing works
“Furthermore, the EC-derived growth factor angiopoietin-2 (ANG2, ANGPT2), which is up-regulated in diseases associated with inflammation and vascular leakage, synergizes with multiple inflammatory agents, promoting endothelial permeability (6, 7).”
BackgroundEffects of a synthetic PEG-ylated Tie-2 agonist peptide on endotoxemic lung injury and mortality
David, S., Ghosh, C. C., Kümpers, P., Shushakova, N., Van Slyke, P., Khankin, E. V., Karumanchi, S. A., Dumont, D., & Parikh, S. M. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00459.2010 · Cited by 96 · see citing works
Self-citationEndothelial Permeability and Hemostasis in Septic Shock
Hou, P. C., Filbin, M. R., Wang, H., Ngo, L., Huang, D. T., Aird, W. C., Yealy, D. M., Angus, D. C., Kellum, J. A., & Shapiro, N. I. (2017) · Chest · doi:10.1016/j.chest.2017.01.010 · Cited by 97 · see citing works
Jumping the barrier: VE‐cadherin, VEGF and other angiogenic modifiers in cancer
Le Guelte, A., Dwyer, J., & Gavard, J. (2011) · Biology of the Cell · doi:10.1042/bc20110069 · Cited by 91 · see citing works
Regulation of angiopoietin expression by bacterial lipopolysaccharide
Mofarrahi, M., Nouh, T., Qureshi, S., Guillot, L., Mayaki, D., & Hussain, S. N. A. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00449.2007 · Cited by 60 · see citing works
Clajus, C., Lukasz, A., David, S., Hertel, B., Lichtinghagen, R., Parikh, S. M., Simon, A., Ismail, I., Haller, H., & Kümpers, P. (2012) · Cytokine · doi:10.1016/j.cyto.2012.04.002 · Cited by 44 · see citing works
Self-citationCharan, M., Dravid, P., Cam, M., Setty, B., Roberts, R. D., Houghton, P. J., & Cam, H. (2020) · Oncotarget · doi:10.18632/oncotarget.27433 · Cited by 41 · see citing works
Angiopoietin‐2 mediates thrombin‐induced monocyte adhesion and endothelial permeability
Rathnakumar, K., Savant, S., Giri, H., Ghosh, A., Fisslthaler, B., Fleming, I., Ram, U., Bera, A. K., Augustin, H. G., & Dixit, M. (2016) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13376 · Cited by 27 · see citing works
- Authors
- Parikh, S. M., Mammoto, T., Schultz, A., Yuan, H.-T., Christiani, D., Karumanchi, S. A., & Sukhatme, V. P.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Corresponding author
- Sukhatme, Vikas P
- Venue
- PLoS Medicine
- Publisher
- Public Library of Science (PLoS)
- Published
- 2006-01-24
- Volume
- 3
- Issue
- 3
- Pages
- e46
- ISSN
- 1549-1277 (ISSN-L)
- 1549-1676
- PMC
- PMC1334221
- OpenAlex
- W2157225099
- Cited by
- 527
- References
- 63
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- FWCI
- 21.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
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- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- angiopoietin-2, sepsis, acute respiratory distress syndrome, sepsis-associated lung injury, endothelial barrier disruption, Tie2 receptor, angiopoietin-1, myosin light chain phosphorylation, pulmonary congestion
- MeSH terms
- Aged, Animals, Blood Vessels, Capillary Permeability, Convalescence, Female, Humans, Lung, Male, Pulmonary Gas Exchange, Up-Regulation, Protein Serine-Threonine Kinases, Sepsis, Angiopoietin-1, Angiopoietin-2, Endothelial Cells, Receptor, TIE-2, Intracellular Signaling Peptides and Proteins, Mice, rho-Associated Kinases
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