Document Detail

Downregulation of angiotensin converting enzyme II is associated with pacing-induced sustained atrial fibrillation.
MedLine Citation:
PMID:  17254576     Owner:  NLM     Status:  MEDLINE    
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.
Chun-Hsu Pan; Jiunn-Lee Lin; Ling-Ping Lai; Chien-Lung Chen; Shoei K Stephen Huang; Chih-Sheng Lin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-17
Journal Detail:
Title:  FEBS letters     Volume:  581     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-30     Completed Date:  2007-03-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  526-34     Citation Subset:  IM    
Department of Biological Science and Technology, National Chiao Tung University, 75 Po-Ai Street, Hsinchu 30005, Taiwan.
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MeSH Terms
Atrial Fibrillation / enzymology*,  genetics*,  pathology
Base Sequence
DNA Primers / genetics
Disease Models, Animal
Heart Atria / pathology
MAP Kinase Signaling System
Models, Cardiovascular
Peptidyl-Dipeptidase A / genetics*,  metabolism*
RNA, Messenger / genetics,  metabolism
Signal Transduction
Sus scrofa
Reg. No./Substance:
0/DNA Primers; 0/RNA, Messenger; EC A; EC 3.4.17.-/angiotensin converting enzyme 2

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