New Insights into Molecular Mechanisms of Atrial Fibrillation: Are We Approaching Possible Novel Pharmacological Principles for Treating This Disorder?

Atrial fibrillation (AF) is associated with significant electrophysiological, structural and molecular alterations of atrial tissue. Some of these changes (e.g. interstitial fibrosis, atrial dilation) provide a proarrhythmogenic substrate which favors the occurrence of AF, although not all of these changes are primarily induced by the arrhythmia itself. Activation of several tissue proteases seems to be of particular importance for the development of structural atrial changes. An increased activation of the atrial angiotensin II system contributes to the development of interstitial atrial fibrosis, which induces proarrhythmic alterations in atrial conduction. Thus, inhibition of the angiotensin-converting enzyme or blockage of angiotensin II receptors may offer a novel antiarrhythmic approach to prevent AF, in particular in patients with concomitant cardiovascular diseases. This review will describe the role and regulation of the atrial angiotensin II system and other molecular signal transduction systems which may have the potential to provide new pharmacological targets for the therapy of AF.