Increased connective tissue growth factor expression in a rat model of chronic heart allograft rejection.
OBJECTIVE
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.


CONCLUSIONS
CTGF is expressed in cardiomyocytes in CAV. Increased expression of CTGF in cardiac allografts is associated with development of CAV and fibrosis formation.
Yuan
Yun-Chang
YC
Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. yuanyunchang1405@126.com
Xia
Zhen-Kun
ZK
Mu
Jing-Jing
JJ
Zhang
Qing-Chun
QC
Yin
Bang-Liang
BL
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis*; D004195:Disease Models, Animal; D018450:Disease Progression; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D016027:Heart Transplantation; D007150:Immunohistochemistry; D008297:Male; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014184:Transplantation, Homologous
D015415:Biomarkers; D055513:Connective Tissue Growth Factor