PAH (pulmonary arterial hypertension) is a debilitating and life-threatening disease, often affecting young people. We specifically expressed human MMP-1 (matrix metalloproteinase-1) in mouse macrophages and examined its effects in attenuating the decompensating features of MCT (monocrotaline)-induced PAH. Measurement of RV (right ventricular) pressure revealed a 2.5-fold increase after treatment with MCT, which was reduced to 1.5-fold in MMP-1 transgenic mice. There was conspicuous pulmonary inflammation with chronic infiltration of mononuclear cells after the administration of MCT, which was significantly diminished in transgenic mice. Furthermore, transgenic mice showed decreased collagen deposition compared with WT (wild-type). Staining for Mac-3 (macrophage-3) and α-SMA (α-smooth muscle actin) revealed extensive infiltration of macrophages and medial hypertrophy of large pulmonary vessels with complete occlusion of small arteries respectively. These changes were markedly reduced in MMP-1 transgenic mice compared with WT. Western blotting for molecules involved in cell multiplication and proliferation depicted a significant decrease in the lung tissue of transgenic mice after the treatment with MCT. In conclusion, the present study demonstrated that transgenic expression of human MMP-1 decreased proliferation of smooth muscle cells and prevented excessive deposition of collagen in the pulmonary arterial tree. Our results indicate that up-regulation of MMP-1 could attenuate the debilitation of human PAH and provide an option for therapeutic intervention.
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Research Article|
September 20 2011
Transgenic expression of human matrix metalloproteinase-1 attenuates pulmonary arterial hypertension in mice
Joseph George;
Joseph George
1
1Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, U.S.A.
Correspondence: Dr Joseph George (email joseph.george@mssm.edu or jgeorge40@hotmail.com).
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Jie Sun;
Jie Sun
1Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, U.S.A.
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Jeanine D'Armiento
Jeanine D'Armiento
1Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, U.S.A.
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Publisher: Portland Press Ltd
Received:
June 07 2011
Revision Received:
July 21 2011
Accepted:
July 27 2011
Accepted Manuscript online:
July 27 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 122 (2): 83–92.
Article history
Received:
June 07 2011
Revision Received:
July 21 2011
Accepted:
July 27 2011
Accepted Manuscript online:
July 27 2011
Connected Content
A retraction has been published:
Retraction: Transgenic expression of human matrix metalloproteinase-1 attenuates pulmonary arterial hypertension in mice
Citation
Joseph George, Jie Sun, Jeanine D'Armiento; Transgenic expression of human matrix metalloproteinase-1 attenuates pulmonary arterial hypertension in mice. Clin Sci (Lond) 1 January 2012; 122 (2): 83–92. doi: https://doi.org/10.1042/CS20110295
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