| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Centre for Respiratory Research, University College London, London, United Kingdom
2 Institute of Pharmacology, Christian-Albrechts University of Kiel, Kiel, Germany
* To whom correspondence should be addressed. E-mail: richard.marshall{at}ucl.ac.uk.
Angiotensin II (Ang II) generated by the activation of local renin-angiotensin systems is believed to play an important role in tissue repair and remodelling, in part via transforming growth factor beta (TGF
). Angiotensin converting enzyme (ACE) inhibitors have been shown to abrogate experimental lung injury via a number of potential mechanisms, however, a fibroproliferative role for Ang II in the lung has not previously been characterized. We therefore hypothesized that following lung injury, Ang II would stimulate fibroblast procollagen synthesis and promote lung collagen deposition. In vitro, Ang II was a potent inducer of procollagen production in human lung fibroblasts via activation of the type 1 receptor and via the autocrine action of TGF. Following bleomycin-induced lung injury in rats, an increase in lung Ang II concentration was observed by day three that preceded increases in lung collagen and was maintained until sacrifice at day 21. The administration of an ACE inhibitor (Ramipril) reduced angiotensin converting enzyme activity, Ang II concentration, TGFexpression and collagen deposition. Losartan (a type 1 Ang II receptor antagonist) also attenuated the increase in TGF expression and lung collagen deposition. These observations suggest that Ang II, possibly generated locally within the lung, may play an important role in the fibrotic response to acute lung injury, at least in part via TGF. ACE inhibitors and receptor antagonists, already widely used clinically, should be assessed as potential new therapies for fibrotic lung disease.
This article has been cited by other articles:
|
|
 |
|
  R. M. Wosten-van Asperen, R. Lutter, J. J. Haitsma, M. P. Merkus, J. B. van Woensel, C. M. van der Loos, S. Florquin, B. Lachmann, and A. P. Bos ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin Eur. Respir. J., February 1, 2008; 31(2): 363 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Konigshoff, A. Wilhelm, A. Jahn, D. Sedding, O. V. Amarie, B. Eul, W. Seeger, L. Fink, A. Gunther, O. Eickelberg, et al. The Angiotensin II Receptor 2 Is Expressed and Mediates Angiotensin II Signaling in Lung Fibrosis Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 640 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Martin, J. A. Buckenberger, J. Jiang, G. E. Malana, D. L. Knoell, D. S. Feldman, and T. S. Elton TGF-beta1 stimulates human AT1 receptor expression in lung fibroblasts by cross talk between the Smad, p38 MAPK, JNK, and PI3K signaling pathways Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L790 - L799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Jerng, Y.-C. Hsu, H.-D. Wu, H.-Z. Pan, H.-C. Wang, C.-T. Shun, C.-J. Yu, and P.-C. Yang Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model Thorax, June 1, 2007; 62(6): 527 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, M. Molina-Molina, A. Abdul-Hafez, J. Ramirez, A. Serrano-Mollar, A. Xaubet, and B. D. Uhal Extravascular sources of lung angiotensin peptide synthesis in idiopathic pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L887 - L895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Molina-Molina, A Serrano-Mollar, O Bulbena, L Fernandez-Zabalegui, D Closa, A Marin-Arguedas, A Torrego, J Mullol, C Picado, and A Xaubet Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin E2 synthesis Thorax, July 1, 2006; 61(7): 604 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. I. Chaudhary, A. Schnapp, and J. E. Park Pharmacologic Differentiation of Inflammation and Fibrosis in the Rat Bleomycin Model Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 769 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. I. Bechara, A. Pelaez, A. Palacio, P. C. Joshi, C. M. Hart, L. A. S. Brown, R. Raynor, and D. M. Guidot Angiotensin II mediates glutathione depletion, transforming growth factor-{beta}1 expression, and epithelial barrier dysfunction in the alcoholic rat lung Am J Physiol Lung Cell Mol Physiol, September 1, 2005; 289(3): L363 - L370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Krick, B. G. Eul, J. Hanze, R. Savai, F. Grimminger, W. Seeger, and F. Rose Role of Hypoxia-Inducible Factor-1{alpha} in Hypoxia-Induced Apoptosis of Primary Alveolar Epithelial Type II Cells Am. J. Respir. Cell Mol. Biol., May 1, 2005; 32(5): 395 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Keogh, J. Standing, G. C. Kane, A. Terzic, and A. H. Limper Angiotensin II antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice Eur. Respir. J., April 1, 2005; 25(4): 708 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Whitsett, C. J. Bachurski, K. C. Barnes, P. A. Bunn Jr., L. M. Case, D. N. Cook, D. Crooks, M. W. Duncan, L. Dwyer-Nield, R. C. Elston, et al. Functional Genomics of Lung Disease Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2/S1): S1 - S81. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
