The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Cell-based Angiopoietin-1 Gene Therapy for Acute Lung Injury
Abstract
Rationale: The acute respiratory distress syndrome is a significant cause of morbidity and mortality in critically ill patients. Angiopoietin-1 (Ang-1), a ligand for the endothelial Tie2 receptor, is an endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte–endothelium interactions. Objectives: We hypothesized that Ang-1 counteracts vascular inflammation and pulmonary vascular leak in experimental acute lung injury. Methods: We used cell-based gene therapy in a rat model of ALI. Transgenic mice overexpressing Ang-1 or deficient in the Tie2 receptor were also studied to better elucidate the mechanisms of protection. Measurements and Main Results: The present report provides data that support a strong protective role for the Ang-1/Tie2 system in two experimental models of LPS-induced acute lung injury. In a rat model, cell-based Ang-1 gene transfer improved morphological, biochemical, and molecular indices of lung injury and inflammation. These findings were confirmed in a gain-of-function conditional, targeted transgenic mouse model, in which Ang-1 reduced endothelial cell activation and the expression of adhesion molecules, associated with a marked improvement in airspace inflammation and intraalveolar septal thickening. Moreover, heterozygous Tie2-deficient mice demonstrated enhanced evidence of lung injury and increased early mortality. Conclusions: These results support a critical role for the Ang-1/Tie2 axis in modulating the pulmonary vascular response to lung injury and suggest that Ang-1 therapy may represent a potential new strategy for the treatment and/or prevention of acute respiratory distress syndrome in critically ill patients.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Such upregulation may have important clinical implications since VEGF and Ang-1 have been shown to play pivotal roles in angiogenesis, alveolar development, and treatment of acute lung injury (ALI) [8, 57–60].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [60]
Citations
Cites
Bernard, G. R., Artigas, A., Brigham, K. L., Carlet, J., Falke, K., Hudson, L., Lamy, M., Legall, J. R., Morris, A., & Spragg, R. (1994) · American journal of respiratory and critical care medicine · doi:10.1164/ajrccm.149.3.7509706 · Cited by 6,746
Incidence and Outcomes of Acute Lung Injury
Rubenfeld, G. D., Caldwell, E., Peabody, E., Weaver, J., Martin, D. P., Neff, M., Stern, E. J., & Hudson, L. D. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050333 · Cited by 3,684
Requisite Role of Angiopoietin-1, a Ligand for the TIE2 Receptor, during Embryonic Angiogenesis
Suri, C., Jones, P. F., Patan, S., Bartunkova, S., Maisonpierre, P. C., Davis, S. H., Sato, T. N., & Yancopoulos, G. D. (1996) · Cell · doi:10.1016/s0092-8674(00)81813-9 · Cited by 2,872
Endothelial cells in physiology and in the pathophysiology of vascular disorders.
Cines, D. B., Pollak, E. S., Buck, C. A., Loscalzo, J., Zimmerman, G. A., McEver, R. P., Pober, J. S., Wick, T. M., Konkle, B. A., Schwartz, B. S., et al. (1998) · PubMed · doi:10.1182/blood.v91.10.3527 · Cited by 2,246
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
Circulating adhesion molecules in disease
Gearing, A. J. H., & Newman, W. (1993) · Immunology Today · doi:10.1016/0167-5699(93)90267-o · Cited by 1,371
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
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 1,314
Riley, S., Fraser, C., Donnelly, C. A., Ghani, A. C., Abu-Raddad, L. J., Hedley, A. J., Leung, G. M., Ho, L., Lam, T.-H., Thach, T., et al. (2003) · Science · doi:10.1126/science.1086478 · Cited by 1,152
Choi, A. M., & Alam, J. (1996) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.15.1.8679227 · Cited by 1,126
Dumont, D. J., Gradwohl, G., Fong, G. H., Puri, M. C., Gertsenstein, M., Auerbach, A., & Breitman, M. L. (1994) · Genes & Development · doi:10.1101/gad.8.16.1897 · Cited by 985
Self-citationBiological Markers of Acute Lung Injury: Prognostic and Pathogenetic Significance
Pittet, J., Mackersie, R. C., Martin, T. R., & Matthay, M. A. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.155.4.9105054 · Cited by 588
Adult Respiratory-Distress Syndrome
Rinaldo, J. E., & Rogers, R. M. (1982) · New England Journal of Medicine · doi:10.1056/nejm198204153061504 · Cited by 563
The Acute Respiratory Distress Syndrome
Kollef, M. H., & Schuster, D. P. (1995) · New England Journal of Medicine · doi:10.1056/nejm199501053320106 · Cited by 551
Epidemiology, transmission dynamics and control of SARS: the 2002–2003 epidemic
Anderson, R. M., Fraser, C., Ghani, A. C., Donnelly, C. A., Riley, S., Ferguson, N. M., Leung, G. M., Lam, T. H., & Hedley, A. J. (2004) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.2004.1490 · Cited by 509
Gamble, J. R., Drew, J., Trezise, L., Underwood, A., Parsons, M., Kasminkas, L., Rudge, J. S., Yancopoulos, G. D., & Vadas, M. A. (2000) · Circulation Research · doi:10.1161/01.res.87.7.603 · Cited by 501
Zhao, Y. D., Courtman, D. W., Deng, Y., Kugathasan, L., Zhang, Q., & Stewart, D. J. (2005) · Circulation Research · doi:10.1161/01.res.0000157672.70560.7b · Cited by 469
Self-citationPapapetropoulos, A., García‐Cardeña, G., Dengler, T. J., Maisonpierre, P. C., Yancopoulos, G. D., & Sessa, W. C. (1999) · PubMed · Cited by 418
Kim, I., Moon, S.-O., Park, S. K., Chae, S., & Koh, G. Y. (2001) · Circulation Research · doi:10.1161/hh1801.097034 · Cited by 368
Markers of endothelial damage in organ dysfunction and sepsis
Reinhart, K., Bayer, O., Brunkhorst, F. M., & Meisner, M. (2002) · Critical Care Medicine · doi:10.1097/00003246-200205001-00021 · Cited by 319
Pulmonary endothelium in acute lung injury: from basic science to the critically ill
Orfanos, S. E., Mavrommati, I., Korovesi, I., & Roussos, C. (2004) · Intensive Care Medicine · doi:10.1007/s00134-004-2370-x · Cited by 241
Angiopoietin‐1 is an apoptosis survival factor for endothelial cells
Kwak, H. J., So, J.-N., Lee, S. J., Kim, I., & Koh, G. Y. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00378-6 · Cited by 238
Increased Circulating Endothelial Progenitor Cells Are Associated with Survival in Acute Lung Injury
Burnham, E. L., Taylor, W. R., Quyyumi, A. A., Rojas, M., Brigham, K. L., & Moss, M. M. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200410-1325oc · Cited by 227
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
Protective Role of Angiopoietin-1 in Experimental Pulmonary Hypertension
Zhao, Y. D., Campbell, A., Robb, M. J., Ng, D., & Stewart, D. J. (2003) · Circulation Research · doi:10.1161/01.res.0000070587.79937.f0 · Cited by 172
Self-citationAngiopoietin‐1 inhibits endothelial permeability, neutrophil adherence and IL‐8 production
Pizurki, L., Zhou, Z., Glynos, K., Roussos, C., & Papapetropoulos, A. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705259 · Cited by 152
Novel isoforms of murine intercellular adhesion molecule-1 generated by alternative RNA splicing.
King, P. D., Sandberg, E. T., Selvakumar, A., Fang, P., Beaudet, A. L., & Dupont, B. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.11.6080 · Cited by 150
Angiogenic growth factors in the pathophysiology of a murine model of acute lung injury
Karmpaliotis, D. I., Kosmidou, I., Ingenito, E. P., Hong, K., Malhotra, A., Sunday, M. E., & Haley, K. J. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00048.2002 · Cited by 141
Resistance to Endotoxin Shock in Transgenic Mice Overexpressing Endothelial Nitric Oxide Synthase
Yamashita, T., Kawashima, S., Ohashi, Y., Ozaki, M., Ueyama, T., Ishida, T., Inoue, N., Hirata, K., Akita, H., & Yokoyama, M. (2000) · Circulation · doi:10.1161/01.cir.101.8.931 · Cited by 140
Endothelium-derived mediators and hypoxic pulmonary vasoconstriction
Aaronson, P. I., Robertson, T. P., & Ward, J. P. T. (2002) · Respiratory Physiology & Neurobiology · doi:10.1016/s1569-9048(02)00053-8 · Cited by 120
Endothelial Activation in ARDS
Zimmerman, G. A., Albertine, K. H., Carveth, H., Gill, E. A., Grissom, C. K., Hoidal, J. R., Imaizumi, T., Maloney, C. G., McIntyre, T. M., Michael, J. R., et al. (1999) · CHEST Journal · doi:10.1378/chest.116.suppl_1.18s · Cited by 113
Maître, B., Boussat, S., Jean, D., Gouge, M., Brochard, L. J., HOUSSET, B., Adnot, S., & Delclaux, C. (2001) · European Respiratory Journal · doi:10.1183/09031936.01.00074701 · Cited by 104
Pathology of the Adult Respiratory Distress Syndrome
Meyrick, B. O. (1986) · Critical Care Clinics · doi:10.1016/s0749-0704(18)30589-x · Cited by 102
Agouridakis, P., Kyriakou, D., Alexandrakis, M. G., Prekates, A. A., Perisinakis, K., Karkavitsas, N. S., & Bouros, D. E. (2002) · Respiratory Research · doi:10.1186/rr193 · Cited by 98
Gando, S., Kameue, T., Matsuda, N., Sawamura, A., Hayakawa, M., & Kato, H. (2004) · Inflammation · doi:10.1023/b:ifla.0000049049.81688.fe · Cited by 94
The role of the endothelium in modulating vascular control in sepsis and related conditions
Wort, S. J., & Evans, T. W. (1999) · British Medical Bulletin · doi:10.1258/0007142991902286 · Cited by 90
Angiopoietin-1 Inhibits Irradiation- and Mannitol-Induced Apoptosis in Endothelial Cells
Kwak, H. J., Lee, S. J., Lee, Y.-H., Ryu, C. H., Koh, K. N., Choi, H. Y., & Koh, G. Y. (2000) · Circulation · doi:10.1161/01.cir.101.19.2317 · Cited by 89
Microvascular Regeneration in Established Pulmonary Hypertension by Angiogenic Gene Transfer
Zhao, Y. D., Courtman, D. W., Ng, D. S., Robb, M. J., Deng, Y., Trogadis, J. E., Han, R. N. N., & Stewart, D. J. (2006) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2005-0115oc · Cited by 89
Self-citationRole of P-Selectin and ICAM-1 in Pancreatitis-Induced Lung Inflammation in Rats
Folch‐Puy, E., Salas, A., Panés, J., Gelpı́, E., Roselló‐Catafau, J., Anderson, D. C., Navarro, S., Pique, J. M., Fernández‐Cruz, L., & Closa, D. (1999) · Annals of Surgery · doi:10.1097/00000658-199912000-00008 · Cited by 88
Endothelin peptides: Biological actions and pathophysiological significance in the lung
Filep, J. G. (1993) · Life Sciences · doi:10.1016/0024-3205(93)90131-l · Cited by 84
Functions of Tie1 and Tie2 Receptor Tyrosine Kinases in Vascular Development
Partanen, J. M., & Dumont, D. (1999) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-59953-8_8 · Cited by 74
Self-citationAdult respiratory distress syndrome — an update
Hasleton, & Roberts (1999) · Histopathology · doi:10.1046/j.1365-2559.1999.00700.x · Cited by 67
Conditional Transgene Expression in Endothelial Cells
Sarao, R., & Dumont, D. (1998) · Transgenic Research · doi:10.1023/a:1008837410485 · Cited by 47
Self-citationRole of E-selectin in bleomycin induced lung fibrosis in mice
Azuma, A. (2000) · Thorax · doi:10.1136/thorax.55.2.147 · Cited by 46
Komatsu, S., Flores, S., Gerritsen, M. E., Anderson, D. C., & Granger, D. N. (1997) · Europe PMC (PubMed Central) · Cited by 44
Neutrophils Mediate Pulmonary Vasomotor Dysfunction in Endotoxin-induced Acute Lung Injury
Sheridan, B. C., McIntyre, R. C., Moore, E. E., Meldrum, D. R., Agrafojo, J., & Fullerton, D. A. (1997) · doi:10.1097/00005373-199703000-00005 · Cited by 41
Role of Angiopoietin-1 in Experimental and Human Pulmonary Arterial Hypertension
Kugathasan, L., Dutly, A., Zhao, Y. D., Deng, Y., Robb, M. J., Keshavjee, S. H., & Stewart, D. J. (2005) · CHEST Journal · doi:10.1378/chest.128.6_suppl.633s · Cited by 36
Self-citationRegulation of endothelin-1 by angiopoietin-1: implications for inflammation.
McCarter, S. D., Lai, P. F. H., Suen, R. S., & Stewart, D. J. (2006) · PubMed · Cited by 35
Self-citationAngiopoietin 1 expression levels in the myocardium direct coronary vessel development
Ward, N. L., Slyke, P. V., Sturk, C., Cruz, M., & Dumont, D. (2004) · Developmental Dynamics · doi:10.1002/dvdy.10479 · Cited by 35
Self-citationRound Table Conference: Acute Lung Injury
(1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.158.2.15823 · Cited by 33
Fishman, A. P., Fishman, M. C., Freeman, B. A., Gimbrone, M. A., Rabinovitch, M., ROBINSON, D., & GAIL, D. B. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.158.2.9803084 · Cited by 31
Fredenburgh, L. E., Baron, R. M., Carvajal, I. M., Mouded, M., Macias, A. A., Ith, B., & Perrella, M. A. (2005) · PubMed · Cited by 29
Guimarães, C. L., Da-Silva, S., Couture, R., & Rae, G. A. (2000) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-200036051-00107 · Cited by 20
Is Cell Therapy in Acute Lung Injury a Realistic Dream?
Kubo, H. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2507006 · Cited by 4
Research works printed but not linked: 10
- 1998, Blood, 91, 3527
- 1999, Lab Invest, 79, 213
- 2004, Circulation, 110(Suppl III), 296
- 2005, Proc Am Thorac Soc, 2, A888
- 2006, Proc Am Thorac Soc, 3, A640
- 2006, Exp Biol Med (Maywood), 231, 985
- 2002, Respir Res, 3, 25, 10.1186/rr190 · DOI
- 2005, Cell Mol Biol, 51, 513
- 1999, Curr Top Microbiol Immunol, 237, 159
- 1997, Am J Pathol, 151, 205
Cited by
Sorted by citations
Mei, S. H. J., McCarter, S. D., Deng, Y., Parker, C. H., Liles, W. C., & Stewart, D. J. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040269 · Cited by 623
Self-citationConcise Review: Mesenchymal Stem Cells for Acute Lung Injury: Role of Paracrine Soluble Factors
Lee, J. W., Fang, X., Krasnodembskaya, A. D., Howard, J. P., & Matthay, M. A. (2011) · Stem Cells · doi:10.1002/stem.643 · Cited by 437
The value of the lipopolysaccharide-induced acute lung injury model in respiratory medicine
Chen, H., Bai, C., & Wang, X. (2010) · Expert Review of Respiratory Medicine · doi:10.1586/ers.10.71 · Cited by 413
Stem Cells and Cell Therapies in Lung Biology and Lung Diseases
Weiss, D. J., Kolls, J. K., Ortiz, L. A., Panoskaltsis‐Mortari, A., & Prockop, D. J. (2008) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200804-037dw · Cited by 308
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
Metadata
- Authors
- 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., Dumont, D. J., & Stewart, D. J.
- Affiliations
- St. Michael's Hospital (CA)
- Sunnybrook Research Institute (CA)
- ORCID
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05
- Volume
- 175
- Issue
- 10
- Pages
- 1014-1026
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2038968218
- Cited by
- 154
- References
- 54
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 4 · 2018: 11 · 2017: 4 · 2016: 9 · 2015: 9 · 2014: 4 · 2013: 11 · 2012: 11
- FWCI
- 12.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- angiopoietin-1, Tie2 receptor, acute lung injury, acute respiratory distress syndrome, cell-based gene therapy, endothelial inflammation, leukocyte-endothelial adhesion, lipopolysaccharide-induced lung injury, endothelial activation, adhesion molecules, transgenic mouse model
- MeSH terms
- Animals, Cell Adhesion, Female, Fibroblasts, Lipopolysaccharides, Male, Mice, Transgenic, Rats, Inbred F344, Respiratory Distress Syndrome, Genetic Therapy, Cell Adhesion Molecules, Gene Expression, Cytokines, Angiopoietin-1, Receptor, TIE-2, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
