Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation
Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation
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DOI：
10.1016/s0735-1097(00)00611-2
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发表时间：
2000-05-01
影响因子：
24
通讯作者：
Lendeckel, U
中科院分区：
文献类型：
--
作者：
Goette, A;Staack, T;Lendeckel, U
目的探讨心房颤动(房颤)患者心房组织中细胞外信号调节蛋白ERK1/ERK2和血管紧张素转换酶(ACE)的表达变化。然而，心房纤维化发生的分子机制尚不清楚。方法对43例心脏直视手术患者的心房组织标本进行检测。慢性持续性房颤(CAF)17例，阵发性房颤(PAF)8例，无房颤病史18例。从定量逆转录聚合酶链式反应(RT-PCR)、蛋白(免疫印迹技术)和心房组织(免疫组织化学)水平分析ERK的表达。结果CAF患者ERK2-mRNA表达增加(75+/-20U vs窦性心律：31+/-25U；p<；0.05)。与窦性心律患者相比，房颤患者激活的ERK1/ERK2和MEK1/2增加到150%以上。CAF与PAF之间无明显差异。血管紧张素转换酶在CAF中的表达增加3倍。在接受血管紧张素转换酶抑制剂治疗的患者中，激活的ERK1/ERK2数量减少。房颤患者心房间质细胞ERK1/ERK2表达增加，心房纤维化明显。结论房颤患者心房间质细胞ERK1/ERK2活性增加可能是房颤患者心房纤维化发生的分子机制之一。这些发现可能对房颤的治疗有重要影响。(C)2000年由美国心脏病学会颁发。
OBJECTIVES The purpose of this study was to determine whether atrial expression of the extracellular signal-regulated kinases Erk1/Erk2 and of the angiotensin-converting enzyme (ACE) is altered in patients with atrial fibrillation (AF).BACKGROUND Recent studies have demonstrated that atrial fibrosis can provide a pathophysiologic substrate for AF. However, the molecular mechanisms responsible for the development of atrial fibrosis are unclear.METHODS Atrial tissue samples of 43 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (greater than or equal to 6 months; CAF), 8 patients had paroxysmal AF (PAF) and 18 patients had no history of AF. Erk expression was analyzed at the mRNA (quantitative reverse transcription polymerase chain reaction), the protein (immunoblot techniques) and atrial tissue (immunohistochemistry) levels. Erk-activating kinases (MEK1/2) and ACE were analyzed by immunoblot techniques.RESULTS Increased amounts of Erk2-mRNA were found in patients with CAF (75 +/- 20 U vs. sinus rhythm: 31 +/- 25 U; p < 0.05). Activated Erk1/Erk2 and MEK1/2 were increased to more than 150% in patients with AF compared to patients with sinus rhythm. No differences between CAF and PAF were found. The expression of ACE was three-fold increased during CAF. Amounts of activated Erk1/Erk2 were reduced in patients treated with ACE inhibitors. Patients with AF showed an increased expression of Erk1/Erk2 in interstitial cells and marked atrial fibrosis. CONCLUSIONS An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF. These findings may have important impact on the treatment of AF. (C) 2000 by the American College of Cardiology.