Increased Connective Tissue Growth Factor Expression in a Rat Model of Chronic Heart Allograft Rejection
Chronic rejection limits the long-term success of cardiac transplantation and the underlying cause of the disease is unknown. Connective tissue growth factor (CTGF) is considered as a mitogenic and chemotactic factor for fibroblasts, and is associated with cell proliferation and collagen synthesis....
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Elsevier
2009-03-01
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Series: | Journal of the Formosan Medical Association |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664609600589 |
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author | Yun-Chang Yuan Zhen-Kun Xia Jing-Jing Mu Qing-Chun Zhang Bang-Liang Yin |
author_facet | Yun-Chang Yuan Zhen-Kun Xia Jing-Jing Mu Qing-Chun Zhang Bang-Liang Yin |
author_sort | Yun-Chang Yuan |
collection | DOAJ |
description | Chronic rejection limits the long-term success of cardiac transplantation and the underlying cause of the disease is unknown. Connective tissue growth factor (CTGF) is considered as a mitogenic and chemotactic factor for fibroblasts, and is associated with cell proliferation and collagen synthesis. We evaluated the expression of CTGF in a rat model of heart allograft chronic rejection.
Methods: Intra-abdominal heterotopic heart transplantation was performed from 20 Wistar rats to 20 Sprague–Dawley (SD) rats that received cyclosporine, mycophenolate mofetil and methylprednisolone as immunosuppression. Ten heart allografts were explanted at 2 and 8 weeks postoperatively for analysis of morphologic changes. The hearts from 10 normal Wistar rats served as a control group. Coronary artery density, luminal loss of myocardial coronary arteries, and myocardial fibrosis were measured. The expression of CTGF was studied by immunohistochemistry. Correlation between CTGF expression and development of cardiac allograft vasculopathy (CAV) or fibrosis was studied.
Results: Allografts harvested at 8 weeks postoperatively showed more coronary intimal proliferation, fibrosis and CTGF expression compared with the 2-week allografts (p < 0.05) and the controls (p < 0.01), but the coronary artery density was lower than in the control group (p < 0.05). However, the control group showed negligible CTGF expression. There were strong negative correlations between the gray value of CTGF protein expression and cardiac fibrosis and coronary intimal occlusion (r = −0.734, −0.713; p < 0.01), which demonstrated that CTGF protein expression was positively correlated with cardiac fibrosis and coronary intimal occlusion.
Conclusion: CTGF is expressed in cardiomyocytes in CAV. Increased expression of CTGF in cardiac allografts is associated with development of CAV and fibrosis formation. |
first_indexed | 2024-04-12T19:08:26Z |
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id | doaj.art-ca6dd0e1a92f4baa81622d351340b700 |
institution | Directory Open Access Journal |
issn | 0929-6646 |
language | English |
last_indexed | 2024-04-12T19:08:26Z |
publishDate | 2009-03-01 |
publisher | Elsevier |
record_format | Article |
series | Journal of the Formosan Medical Association |
spelling | doaj.art-ca6dd0e1a92f4baa81622d351340b7002022-12-22T03:19:57ZengElsevierJournal of the Formosan Medical Association0929-66462009-03-01108324024610.1016/S0929-6646(09)60058-9Increased Connective Tissue Growth Factor Expression in a Rat Model of Chronic Heart Allograft RejectionYun-Chang Yuan0Zhen-Kun Xia1Jing-Jing Mu2Qing-Chun Zhang3Bang-Liang Yin4Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Anesthesia, The Second Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, ChinaChronic rejection limits the long-term success of cardiac transplantation and the underlying cause of the disease is unknown. Connective tissue growth factor (CTGF) is considered as a mitogenic and chemotactic factor for fibroblasts, and is associated with cell proliferation and collagen synthesis. We evaluated the expression of CTGF in a rat model of heart allograft chronic rejection. Methods: Intra-abdominal heterotopic heart transplantation was performed from 20 Wistar rats to 20 Sprague–Dawley (SD) rats that received cyclosporine, mycophenolate mofetil and methylprednisolone as immunosuppression. Ten heart allografts were explanted at 2 and 8 weeks postoperatively for analysis of morphologic changes. The hearts from 10 normal Wistar rats served as a control group. Coronary artery density, luminal loss of myocardial coronary arteries, and myocardial fibrosis were measured. The expression of CTGF was studied by immunohistochemistry. Correlation between CTGF expression and development of cardiac allograft vasculopathy (CAV) or fibrosis was studied. Results: Allografts harvested at 8 weeks postoperatively showed more coronary intimal proliferation, fibrosis and CTGF expression compared with the 2-week allografts (p < 0.05) and the controls (p < 0.01), but the coronary artery density was lower than in the control group (p < 0.05). However, the control group showed negligible CTGF expression. There were strong negative correlations between the gray value of CTGF protein expression and cardiac fibrosis and coronary intimal occlusion (r = −0.734, −0.713; p < 0.01), which demonstrated that CTGF protein expression was positively correlated with cardiac fibrosis and coronary intimal occlusion. Conclusion: CTGF is expressed in cardiomyocytes in CAV. Increased expression of CTGF in cardiac allografts is associated with development of CAV and fibrosis formation.http://www.sciencedirect.com/science/article/pii/S0929664609600589connective tissue growth factorfibrosisgraft rejectionheart transplantation |
spellingShingle | Yun-Chang Yuan Zhen-Kun Xia Jing-Jing Mu Qing-Chun Zhang Bang-Liang Yin Increased Connective Tissue Growth Factor Expression in a Rat Model of Chronic Heart Allograft Rejection Journal of the Formosan Medical Association connective tissue growth factor fibrosis graft rejection heart transplantation |
title | Increased Connective Tissue Growth Factor Expression in a Rat Model of Chronic Heart Allograft Rejection |
title_full | Increased Connective Tissue Growth Factor Expression in a Rat Model of Chronic Heart Allograft Rejection |
title_fullStr | Increased Connective Tissue Growth Factor Expression in a Rat Model of Chronic Heart Allograft Rejection |
title_full_unstemmed | Increased Connective Tissue Growth Factor Expression in a Rat Model of Chronic Heart Allograft Rejection |
title_short | Increased Connective Tissue Growth Factor Expression in a Rat Model of Chronic Heart Allograft Rejection |
title_sort | increased connective tissue growth factor expression in a rat model of chronic heart allograft rejection |
topic | connective tissue growth factor fibrosis graft rejection heart transplantation |
url | http://www.sciencedirect.com/science/article/pii/S0929664609600589 |
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