Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation
Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation
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DOI：
10.1016/j.cardiores.2005.04.016
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发表时间：
2005-09-01
影响因子：
10.8
通讯作者：
Heidbüchel, H
中科院分区：
文献类型：
--
作者：
Anné, W;Willems, R;Heidbüchel, H
背景：心房颤动（AF）与涉及心房纤维化和心房扩张的细胞外基质重塑相关。血管紧张素 II 介导的途径和基质金属蛋白酶 (MMP) 与这些过程有关。我们的目的是研究伴或不伴 AF 的二尖瓣疾病患者的心房结构重塑以及血管紧张素受体亚型和 MMP 及其抑制剂 (TIMP) 的表达。方法和结果：从接受 CABG 的患者（n = 9，全部为窦性心律 (SR)）或二尖瓣手术患者中采集右心耳和左心耳（RA 和 LA）活检 （MVS；n = 19；9 个具有永久 AF，10 个具有 SR）。 MVS 和 AF 患者的心房明显增大（与 MVS 和 SR 相比：p=0.02；与 CABG 相比：p < 0.01）。 MVS 患者的纤维化程度明显高于对照组 CABG 组。 LA 中 AF 和 SR MVS 组的纤维化均增加，但 RA 中仅 MVS-AF 组纤维化增加。这些 AF 患者的三尖瓣反流明显多于 SR 患者。 MMP-1 在 MVS 患者的 LA 中下调 (p=0.02)，与基本节律（SR 或 AF；p=0.95）无关。在 RA 活检中，MMP-1 仅在 MVS 和 AF 组中下调。与 CABG 患者相比，MVS 患者的 MMP-9 在 RA 和 LA 组中均下调，而 SR 组和 AF 组之间没有差异。 AT-1、AT-2、MMP-2、TIMP-1、-2 和 -4、TNF-α 和 TNF-α 转换酶的蛋白表达在 3 组之间没有显着差异。 结论：LA 和 RA 中二尖瓣疾病期间 NIMP 表达与纤维化之间的一致变化表明 MMT 参与结构性心房重构。 AF 本身不会导致 LA 中纤维化或 MMP 表达的改变。 AF 和 RA 变化之间的关联可能是由于这些患者三尖瓣反流导致的更大的血液动力负荷所致。 (c) 2005 年欧洲心脏病学会。由 Elsevier B.V. 出版。保留所有权利。
Background: Atrial fibrillation (AF) is associated with extracellular matrix remodeling involving atrial fibrosis and atrial dilatation. Angiotensin II mediated pathways and matrix metalloproteinases (MMPs) have been implicated in these processes. Our aim was to study atrial structural remodeling and the expression of the angiotensin receptor subtypes and MMPs and their inhibitors (TIMPs) in patients with mitral valve disease with and without AF.Methods and results: Biopsies from right and left atrial appendages (RA and LA) were taken from patients undergoing CABG (n=9, all in sinus rhythm (SR)) or mitral valve surgery (MVS; n = 19; 9 with permanent AF and 10 in SR). Patients with MVS and AF had significantly larger atria (versus MVS and SR: p=0.02; versus CABG: p < 0.01). The MVS patients had significantly more fibrosis than the control CABG group. Fibrosis was increased in both the AF and SR MVS groups in the LA, but only in the MVS-AF group in the RA. These AF patients had significantly more tricuspid regurgitation than SR patients. MMP-1 was down-regulated in LA of MVS patients (p=0.02) independent of the underlying rhythm (SR or AF; p=0.95). In RA biopsies, MMP-1 was down-regulated only in the MVS and AF group. MMP-9 was down-regulated in the MVS patients compared to CABG both in the RA and LA, and without a difference between the SR and AF groups. Protein expression of AT-1, AT-2, MMP-2, TIMP-1, -2 and -4, TNF-alpha, and TNF-alpha-converting enzyme did not differ significantly between the 3 groups.Conclusions: Concordant changes between NIMP-expression and fibrosis during mitral valve disease, both in LA and RA, suggest involvement of MMT's in structural atrial remodeling. AF itself did not contribute to altered fibrosis or MMP-expression in the LA. The association between AF and RA changes may be precipitated by greater hemodynainic load due to tricuspid regurgitation in these patients. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.