Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation
Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation
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DOI：
10.1016/j.jacc.2003.08.060
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发表时间：
2004-03-03
影响因子：
24
通讯作者：
Chayama, K
中科院分区：
文献类型：
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作者：
Nakano, Y;Niida, S;Chayama, K
本研究旨在探讨基质金属蛋白酶（MMP）-1、-2、-9和金属蛋白酶组织抑制剂（TIMP）-1与心房颤动（AF）时心房结构重构的关系。调节心脏组织细胞外基质周转。方法组织样本来自25例无AF病史的患者，（规则窦性心律[RSR]）和13例接受心脏手术的AF患者（阵发性AF：6例，慢性AF 7例）。采用Western blotting检测MMP-1、-2、-9的表达，采用真实的时间聚合酶链反应（PCR）和酶联免疫吸附试验（ELISA）检测MMP-9和TIMP-1的表达。结果AF组MMP-9活性型表达明显高于RSR组（p < 0.05），而MMP-9潜伏型、MMP-1和MMP-2活性型和潜伏型表达无明显差异。我们还证明，在信使核糖核酸（mRNA）（AF：RSR; 1：1.5）和蛋白质水平（AF：RSR; 3.9 +/- 1.3：1.5 +/- 0.4 ng/mg心房）方面，AF组心房中MMP-9的表达显著高于RSR组。PAF组MMP-9的表达水平也高于RSR组，但两组的左心房直径相似。明胶酶活性与左房内径呈正相关（P < 0.05，R = 0.766）。AF组单核细胞趋化蛋白-1 mRNA的相对表达高于RSR组。免疫组化结果显示，MMP-9主要分布于心房的血管周围和心外膜下。结论：MMP-9在心房颤动时表达增加，可能与心房结构重构和心房扩张有关。
OBJECTIVES The purpose of this study was to determine the relationship between matrix metalloproteinases (MMPs)-1, -2, and -9, and tissue inhibitors of metalloproteinases (TIMP)-1 and the atrial structural remodeling during atrial fibrillation (AF).BACKGROUND Matrix metalloproteinases, a family of proteolytic enzymes and TIMPs, regulate the extracellular matrix turnover in cardiac tissue.METHODS Tissue samples were obtained from 25 patients without a history of AF (regular sinus rhythm [RSR]) and 13 patients with AF (paroxysmal AF: 6, chronic AF 7) undergoing cardiac operations. We performed a western blotting analysis of the MMP-1, -2, and -9, and quantitatively analyzed the expression of the MMP-9 and TIMP-1 by real time polymerase chain reaction and ELISA. The localization of the MMP-9 was investigated by in situ zymography and immunohistochemistry.RESULTS The active form of the MMP-9 was significantly increased in the AF group in comparison to that in the RSR group (p < 0.05), but there were no differences between the groups in the protein level of the latent form of the MMP-9 and active and latent forms of the MMP-1 and MMP-2. We also demonstrated that the expression of the MMP-9 was significantly more increased in the atria of the AF group than in that of the RSR group for both the messenger ribonucleic acid (mRNA) (AF: RSR; 1: 1.5) and protein levels (AF: RSR; 3.9 +/- 1.3: 1.5 +/- 0.4 ng/mg atrium). The expression level of the MMP-9 was also higher in the PAF group than in the RSR group, however, the diameter of the left atrium was similar in both groups. The gelatinase activity and left atrium diameter were positively correlated (p < 0.05, R = 0.766). The relative expression of the mRNA for the monocyte chemoattractant protein-1 was higher in the AF group than in the RSR group. Immunohistochemical analysis revealed that the MMP-9 was distributed within the perivascular area and under the epicardium of the atria.CONCLUSIONS We clearly showed that the expression of the MMP-9 increased in fibrillating atrial tissue, which may have contributed to the atrial structural remodeling and atrial dilatation during AF. (C) 2004 by the American College of Cardiology Foundation.