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).
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.
Atrial tissue samples of 43 patients undergoing open heart surgery were examined.
Seventeen patients had chronic persistent AF (> or =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.
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.
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