|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print June 20, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00919.2001
Submitted on November 1, 2001
Accepted on June 18, 2002
1 Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
2 Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
3 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
4 Tokyo R&D Center, Daiichi Pharmaceutical Co., Tokyo, Japan
* To whom correspondence should be addressed. E-mail: yonemitu{at}pathol1.med.kyushu-u.ac.jp.
Monocyte/macrophage chemoattractant protein-1 (MCP-1), a potent chemoattractant chemokine and an activator for mononuclear cells, may play a role in initiation and/or progression of pulmonary hypertension (PH). To determine if blockade of a systemic MCP-1 signal pathway in vivo may prevent PH, we intramuscularly transduced a naked plasmid encoding 7-N-terminus-deleted dominant negative inhibitor of MCP-1 (7ND MCP-1) gene in monocrotaline-induced PH. We also simultaneously gave a duplicate transfection at 2 week intervals or skeletal muscle-directed in vivo electroporation (EP) to evaluate if a longer or higher expression might be more effective. The intramuscular reporter gene expression was enhanced 10-times over that by EP than by simple injection, and a significant 7ND MCP-1 protein in plasma was detected only in the EP group. 7ND MCP-1 gene transfer significantly inhibited the progression of MCT-induced PH as evaluated by right ventricular systolic pressure, right ventricular hypertrophy, medial hypertrophy of pulumonary arterioles and mononuclear cell infiltration into the lung. Differential effects of longer or higher transgene expression were not apparent. Although the in vivo kinetics of 7ND MCP-1 gene therapy should be studied further, these encouraging results suggest that an anti-inflammatory strategy via blockade of the MCP-1 signal pathway may be an alternative approach to treat subjects with PH.
This article has been cited by other articles:
![]() |
J. Le Pavec, F. Perros, S. Eddahibi, B. Decante, P. Dorfmuller, O. Sitbon, D. Lebrec, M. Humbert, M. Mazmanian, and P. Herve Cirrhosis ameliorates monocrotaline-induced pulmonary hypertension in rats Eur. Respir. J., September 1, 2009; 34(3): 731 - 739. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Ferreira, V. Shenoy, Y. Yamazato, S. Sriramula, J. Francis, L. Yuan, R. K. Castellano, D. A. Ostrov, S. P. Oh, M. J. Katovich, et al. Evidence for Angiotensin-converting Enzyme 2 as a Therapeutic Target for the Prevention of Pulmonary Hypertension Am. J. Respir. Crit. Care Med., June 1, 2009; 179(11): 1048 - 1054. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kimura, K. Egashira, L. Chen, K. Nakano, E. Iwata, M. Miyagawa, H. Tsujimoto, K. Hara, R. Morishita, K. Sueishi, et al. Nanoparticle-Mediated Delivery of Nuclear Factor {kappa}B Decoy Into Lungs Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension Hypertension, May 1, 2009; 53(5): 877 - 883. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. T. Zamanian, G. Hansmann, S. Snook, D. Lilienfeld, K. M. Rappaport, G. M. Reaven, M. Rabinovitch, and R. L. Doyle Insulin resistance in pulmonary arterial hypertension Eur. Respir. J., February 1, 2009; 33(2): 318 - 324. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Schober Chemokines in Vascular Dysfunction and Remodeling Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1950 - 1959. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Sanchez, E. Marcos, F. Perros, E. Fadel, L. Tu, M. Humbert, P. Dartevelle, G. Simonneau, S. Adnot, and S. Eddahibi Role of Endothelium-derived CC Chemokine Ligand 2 in Idiopathic Pulmonary Arterial Hypertension Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 1041 - 1047. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Sawada, Y. Mitani, J. Maruyama, B. H. Jiang, Y. Ikeyama, F. A. Dida, H. Yamamoto, K. Imanaka-Yoshida, H. Shimpo, A. Mizoguchi, et al. A Nuclear Factor-{kappa}B Inhibitor Pyrrolidine Dithiocarbamate Ameliorates Pulmonary Hypertension in Rats Chest, October 1, 2007; 132(4): 1265 - 1274. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Hansmann, R. A. Wagner, S. Schellong, V. A. de Jesus Perez, T. Urashima, L. Wang, A. Y. Sheikh, R. S. Suen, D. J. Stewart, and M. Rabinovitch Pulmonary Arterial Hypertension Is Linked to Insulin Resistance and Reversed by Peroxisome Proliferator-Activated Receptor-{gamma} Activation Circulation, March 13, 2007; 115(10): 1275 - 1284. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Yamaji-Kegan, Q. Su, D. J. Angelini, H. C. Champion, and R. A. Johns Hypoxia-induced mitogenic factor has proangiogenic and proinflammatory effects in the lung via VEGF and VEGF receptor-2 Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1159 - L1168. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Fujii, Y. Yonemitsu, M. Onimaru, M. Tanii, T. Nakano, K. Egashira, T. Takehara, M. Inoue, M. Hasegawa, H. Kuwano, et al. Nonendothelial Mesenchymal Cell-Derived MCP-1 Is Required for FGF-2-Mediated Therapeutic Neovascularization: Critical Role of the Inflammatory/Arteriogenic Pathway Arterioscler Thromb Vasc Biol, November 1, 2006; 26(11): 2483 - 2489. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. R. Stenmark, N. J. Davie, J. T. Reeves, and M. G. Frid Hypoxia, leukocytes, and the pulmonary circulation J Appl Physiol, February 1, 2005; 98(2): 715 - 721. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Lu, H. Shimpo, A. Shimamoto, A. J. Chong, C. R. Hampton, D. J. Spring, M. Yada, M. Takao, K. Onoda, I. Yada, et al. Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats J. Thorac. Cardiovasc. Surg., December 1, 2004; 128(6): 850 - 859. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Shimizu, S. Maruyama, Y. Yuzawa, T. Kato, Y. Miki, S. Suzuki, W. Sato, Y. Morita, H. Maruyama, K. Egashira, et al. Anti-Monocyte Chemoattractant Protein-1 Gene Therapy Attenuates Renal Injury Induced by Protein-Overload Proteinuria J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1496 - 1505. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |