Downregulation of angiotensin converting enzyme II is associated with pacing-induced sustained atrial fibrillation

Pan, Chun-Hsu; Lin, Jiunn-Lee; Lai, Ling-Ping; Chen, Chien-Lung; Stephen Huang, Shoei K.; Lin, Chih-Sheng

doi:10.1016/j.febslet.2007.01.014

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Volume 581, Issue 3 , Pages 526-534, 6 February 2007

Downregulation of angiotensin converting enzyme II is associated with pacing-induced sustained atrial fibrillation

Edited by Lukas Huber

Chun-Hsu Pan
- Department of Biological Science and Technology, National Chiao Tung University, 75 Po-Ai Street, Hsinchu 30005, Taiwan
Jiunn-Lee Lin
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Ling-Ping Lai
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Chien-Lung Chen
- Department of Biological Science and Technology, National Chiao Tung University, 75 Po-Ai Street, Hsinchu 30005, Taiwan
Shoei K. Stephen Huang
- Division of Cardiology, China Medical University Hospital, Taichung, Taiwan
Chih-Sheng Lin
- Department of Biological Science and Technology, National Chiao Tung University, 75 Po-Ai Street, Hsinchu 30005, Taiwan
- Corresponding author. Fax: +886 3 5729288.

Received 26 October 2006; accepted 4 January 2007. published online 17 January 2007.

Abstract

Atrial fibrillation (AF), the most common cardiac arrhythmia, is frequently accompanied by atrial interstitial fibrosis. Angiotensin II (Ang II) dependent signaling pathways have been implicated in interstitial fibrosis during the development of AF. However, Ang II could be further degraded by angiotensin converting enzyme II (ACE2). We examined expression of ACE2 in the fibrillating atria of pigs and its involvement in fibrotic pathogenesis during AF. Nine adult pigs underwent continuous rapid atrial pacing to induce sustained AF and six pigs were sham controls (i.e., sinus rhythm; SR). In the histological examinations, extensive accumulation of extracellular matrix in the interstitial space of the atria, as evidenced by Masson’s trichrome stain, were found in fibrillating atria. The relative amount of collagen type I in the atria with AF was significantly increased as compared with that in the SR. Local ACE activity in the fibrillating atria was also markedly higher than that in the SR subjects. ACE2 gene and protein expression in the AF subjects were significantly decreased compared with those in the SR subjects, whereas expression of mitogen-activated/ERK kinase 1/2 (MEK1/2), extracellular signal-regulated protein kinase 2 (ERK2), and activated ERK2 were significantly greater in the AF subjects. We propose that decreasing ACE2 expression during AF may affect the Ang II-dependent signaling pathway. In addition, our results suggest that atrial fibrosis in AF may be induced by antagonistic regulation between ACE and ACE2 expression.

Abbreviations: ACE, angiotensin converting enzyme, ACE2, angiotensin converting enzyme II, AF, atrial fibrillation, Ang I, angiotensin I, Ang II, angiotensin II, ECM, extracellular matrix, ERK1/2, extracellular signal-regulated kinase 1/2, MAPK, mitogen-activated protein kinase, MEK1/2, mitogen-activated/ERK kinase 1/2, MI, myocardial infarction, RAS, renin-angiotensin system, SR, sinus rhythm