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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)526-534
Number of pages9
JournalFEBS Letters
Volume581
Issue number3
DOIs
Publication statusPublished - Feb 6 2007
Externally publishedYes

Keywords

  • Angiotensin converting enzyme II
  • Atrial fibrillation
  • Extracellular signal-regulated kinase
  • Fibrosis
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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