Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation

被引：85
作者：
Bukowska, A
Lendeckel, U
Hirte, D
Wolke, C
Striggow, F
Röhnert, P
Huth, C
Klein, HU
Goette, A
机构：
[1] Univ Hosp Magdeburg, Div Cardiol, D-39120 Magdeburg, Germany
[2] Univ Hosp Magdeburg, Inst Expt Internal Med, D-39120 Magdeburg, Germany
[3] Univ Hosp Magdeburg, Dept Cardiovasc Surg, D-39120 Magdeburg, Germany
[4] KeyNeurotek, D-39120 Magdeburg, Germany
来源：
CELLULAR AND MOLECULAR LIFE SCIENCES | 2006年 / 63卷 / 03期
关键词：
fibrillation; calcium; calcineurin; hypertrophy; pacing;
D O I：
10.1007/s00018-005-5353-3
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Atrial tachyarrhythmia (AF) alters intracellular calcium homeostasis and induces cellular hypertrophy of atrial myocytes. The impact of the calcium-dependent calcineurin pathway on the development of AF-induced atrial hypertrophy has not yet been analyzed. In this study, atrial tissue samples from patients with sinus rhythm and chronic persistent atrial fibrillation (CAF) were used to determine changes in expression and activity of calcineurin A (CnA), and its relation to CnA-regulated transcription factors NFATc1-4, and hypertrophic markers ANP, troponin I, and beta-MHC. CnA phosphatase activity and CnA beta protein contents were significantly upregulated in patients with CAF. Calcineurin activation led to dephosphorylation, redistribution, and subsequent accumulation of NFATc3 in nuclei during CAF, and expression of hypertrophic genes was increased. CAF-dependent changes were reproduced by ex vivo pacing (2-4 Hz) of human atrial tissue slices. FK506 abolished the hypertrophic response induced by electrical-field stimulation. Atrial tachyarrhythmia causes atrial hypertrophy by activation of the CnA signal pathway, which thereby contributes to structural remodeling of human atria.
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收藏
页码：333 / 342
页数：10
相关论文
共 54 条
  • [1] EXPRESSION OF ATRIAL NATRIURETIC FACTOR GENE IN HEARTS FROM NEONATES OF SPONTANEOUSLY HYPERTENSIVE RATS AND STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS[J]. ARAI, H;NAKAO, K;SAITO, Y;SUGAWARA, A;YAMADA, T;ITOH, H;MUKOYAMA, M;HOSODA, K;SHIRAKAMI, G;MORII, N;SHIONO, S;OHKUBO, H;NAKANISHI, S;IMURA, H. JOURNAL OF HYPERTENSION, 1988
  • [2] Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat[J]. Ausma, J;Wijffels, M;Thone, F;Wouters, L;Allessie, M;Borgers, M. CIRCULATION, 1997(09)
  • [3] Changes in ultrastructural calcium distribution in goat atria during atrial fibrillation[J]. Ausma, J;Dispersyn, GD;Duimel, H;Thoné, F;Donck, LV;Allessie, MA;Borgers, M. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2000(03)
  • [4] Defective T cell development and function in calcineurin Aβ-deficient mice[J]. Bueno, OF;Brandt, EB;Rothenberg, ME;Molkentin, JD. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002(14)
  • [5] Calcineurin and hypertrophic heart disease: novel insights and remaining questions[J]. Bueno, OF;van Rooij, E;Molkentin, JD;Doevendans, PA;De Windt, LJ. CARDIOVASCULAR RESEARCH, 2002(04)
  • [6] CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
  • [7] Epidemiology and natural history of atrial fibrillation: Clinical implications[J]. Chugh, SS;Blackshear, JL;Shen, WK;Hammill, SC;Gersh, BJ. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2001(02)
  • [8] NFAT signaling: Choreographing the social lives of cells[J]. Crabtree, GR;Olson, EN. CELL, 2002
  • [9] Prediction of whole-body metabolic clearance of drugs through the combined use of slices from rat liver, lung, kidney, small intestine and colon[J]. De Kanter, R;Monshouwer, M;Draaisma, AL;De Jager, MH;De Graaf, IAM;Proost, JH;Meijer, DKF;Groothuis, GMM. XENOBIOTICA, 2004(03)
  • [10] DERYCKERE F, 1994, BIOTECHNIQUES, V16, P405
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