Role and significance of connective tissue growth factor expression in a rat model of chronic heart allograft rejection

Yunchang YUAN; Zhenkun XIA; Dianjun WANG; Qingchun ZHANG; Bangliang YIN

ABSTRACT

BACKGROUND:

Chronic rejection limits the long-term success of cardiac transplantation and the underlying causes of the disease are 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.

OBJECTIVE:

To evaluate the role and significance of expression of CTGF in rat chronic rejection heart aliografta.DESIGN, TIME AND

SETTING:

A randomized controlled animal experiment was performed at the Laboratory Animal Center of the Second Xiangya Hospital between April and August 2007.MATERIALS Twenty Wistar rats serving as donors and twenty Sprague-Dawely (SD) rats serving as recipients were included. An additional 10 Wistar rats were included as controls.

METHODS:

After intra-abdominal heterotopic heart transplantations, rats received cyclosporine A, mycophenolate, and methylprednisolone immunosuppression. Ten recipient rats were anesthetized and sacrificed for heart harvesting at 2 and 8 weeks postoperation, respectively.MAIN OUTCOME

MEASURES:

Coronary vessel density, fibrosis grade, and intimal occlusion were observed by hematoxylin-cosin staining and Van Gieson staining. Myocardial fibrosis was semi-quantitatively scored. CTGF expression was detected by immunohistochemistry. The associations between CTGF expression and allograft fibrosis and CAV formation were analyzed.

RESULTS:

Allografts harvested at 8-week post-surgery showed more obvious coronary intimal proliferation, fibrosis and higher CTGF expression compared with the 2-week allografts and the controls (P < 0.05-0.01 ) while the cardiac artery density was lower than the control group (P < 0.05). However, the control group in our study 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), demonstrating that CTGF protein expression was positively correlated with cardiac fibrosis and coronary intimal occlusion.

CONCLUSION:

CTGF is expressed in cardiac myocyte with CAV. The increased expression of CTGF in the cardiac allograft is associated with CAV development and fibrosis formation and is involved in the pathogenesis of cbronic heart rejection