Ke Dan, Xu Chun-xuan, Lin Ya-zhou, Zhang Jian-cheng, Chen Lin, Lin Li-fang, Hu Xi-zhong
Fujian Provincial Research Institute of Cardiovascular Diseases, Fuzhou 350001, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2005 May;33(5):459-63.
To determine the molecular mechanisms involved in atrial fibrosis which occurs in patients with atrial fibrillation (AF) and to investigate their effects on the initiation and maintenance of AF.
The right atrial tissue samples were taken from 73 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients had no history of AF (sinus rhythm group), 9 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA content of collagen type I, collagen type III, MMP-2, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and normalized to beta-actin or GAPDH.
Compared to sinus rhythm group, the mRNA of collagen type I and MMP-2 increased significantly in the persistent AF group (all, P < 0.01), followed by the paroxysmal AF group (all, P < 0.05). The mRNA of collagen type III was slightly higher in both AF groups than in the sinus rhythm group, but the differences were not statistically significant (P > 0.05). The mRNA of TIMP-1, TIMP-2 and TIMP-3 was down-regulated in the persistent AF group (all, P < 0.01, respectively), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P > 0.05). The mRNA of TIMP-4 remained compatible in each group. The mRNA of collagen type I was significantly correlated with left atrial dimension (r = 0.336, P = 0.004) and AF duration (r = 0.339, P = 0.003). The mRNA of MMP-2 was significantly correlated with the mRNA of TIMP-2 (r = -0.326, P = 0.006), the mRNA of collagen type I (r = 0.322, P = 0.006), left atrial dimension (r = 0.300, P = 0.011) and AF duration (r = 0.300, P = 0.010).
The increased level of collagen type I associated with selective downregulation of TIMP-2 and upregulation of MMP-2 gene expression in atrium could be one of the molecular mechanisms of atrial fibrosis during atrial fibrillation, which correlates with the initiation and maintenance of AF.
确定心房颤动（AF）患者发生心房纤维化的分子机制，并研究其对AF起始和维持的影响。
从73例行心脏瓣膜置换手术的风湿性心脏病患者中获取右心房组织样本。34例患者无AF病史（窦性心律组），9例患者有阵发性AF，30例患者有持续性AF。采用半定量逆转录聚合酶链反应（RT-PCR）检测I型胶原、III型胶原、MMP-2、TIMP-1、TIMP-2、TIMP-3和TIMP-4的mRNA含量，并以β-肌动蛋白或GAPDH进行标准化。
与窦性心律组相比，持续性AF组I型胶原和MMP-2的mRNA显著增加（均P < 0.01），其次是阵发性AF组（均P < 0.05）。两组AF患者III型胶原的mRNA均略高于窦性心律组，但差异无统计学意义（P > 0.05）。持续性AF组TIMP-1、TIMP-2和TIMP-3的mRNA下调（均P < 0.01），然而，阵发性AF组的降低趋势未达到统计学意义（P > 0.05）。TIMP-4的mRNA在各组中保持一致。I型胶原的mRNA与左心房内径显著相关（r = 0.336，P = 0.004）和AF持续时间显著相关（r = 0.339，P = 0.003）。MMP-2的mRNA与TIMP-2的mRNA显著相关（r = -0.326，P = 0.006）、与I型胶原的mRNA显著相关（r = 0.322，P = 0.006）、与左心房内径显著相关（r = 0.三十，P = 0.011）和与AF持续时间显著相关（r = 0.三十，P = 0.010）。
心房中I型胶原水平升高与TIMP-2的选择性下调和MMP-2基因表达上调相关，可能是心房颤动期间心房纤维化的分子机制之一，这与AF的起始和维持相关。
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