Xie Ye-qing, Chen Rui-zhen, Yu Yong, Chen Ping, Yang Zhao-hua, Guo Qi, Yang Ying-zhen
Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Dec;37(12):1081-4.
To observe the possible correlation between expression of chromogranin A (CGA) and myocardial fibrosis and investigate the potential role of CGA in the development of myocardial fibrosis in patients with dilated cardiomyopathy (DCM).
Surgical myocardial specimen from 10 DCM patients underwent successful orthotopic cardiac transplantation, and 3 normal myocardial specimen from brain-dead organ donors were obtained. CGA-mRNA, COLI-mRNA, COLIII-mRNA and ADAMTS-1-mRNA were analyzed by real-time PCR. The location and expression of CGA were assessed by immunohistochemistry(INH)with anti-CGA antibody. The collagen specific picrosirius red staining was applied on transversal myocardial slides and the collagen volume fraction (CVF) was calculated. The correlation between CGA and CVF was analyzed.
Cytoplasmic expression of CGA assessed by INH showed large amount of strong positive granules densely arranged in the epicardial and endocardial myocardiocytes in DCM specimen while there was only few sparse granules in the normal myocardium (P < 0.05). CVF was significantly higher in DCM myocardial specimen than that in normal specimen (P < 0.001). CGA-mRNA was significantly correlated with COLI-mRNA (r = 0.729), COLIII-mRNA (r = 0.95) and ADAMTS-1-mRNA (r = 0.665, all P < 0.05). Moreover, collagen deposition location was almost identical with the strong positive expression location of CGA.
We demonstrated for the first time that the deposition of CGA was related with the myocardial fibrosis in DCM heart, therefore, CGA might play an important role by influencing myocardial remodeling and fibrosis in DCM patients.
观察嗜铬粒蛋白A（CGA）表达与心肌纤维化之间的可能相关性，并探讨CGA在扩张型心肌病（DCM）患者心肌纤维化发展中的潜在作用。
获取10例接受原位心脏移植成功的DCM患者的手术心肌标本，以及3例脑死亡器官捐献者的正常心肌标本。采用实时PCR分析CGA-mRNA、COLI-mRNA、COLIII-mRNA和ADAMTS-1-mRNA。用抗CGA抗体通过免疫组织化学（INH）评估CGA的定位和表达。对心肌横切片进行胶原特异性天狼星红染色，并计算胶原体积分数（CVF）。分析CGA与CVF之间的相关性。
通过INH评估的CGA细胞质表达显示，DCM标本的心外膜和心内膜心肌细胞中有大量强阳性颗粒密集排列，而正常心肌中只有少量稀疏颗粒（P<0.05）。DCM心肌标本的CVF显著高于正常标本（P<0.001）。CGA-mRNA与COLI-mRNA（r=0.729）、COLIII-mRNA（r=0.95）和ADAMTS-1-mRNA（r=0.665，均P<0.05）显著相关。此外，胶原沉积位置与CGA的强阳性表达位置几乎相同。
我们首次证明CGA的沉积与DCM心脏的心肌纤维化有关，因此，CGA可能通过影响DCM患者的心肌重塑和纤维化发挥重要作用。
