Abstract 12755: Heart-specific Overexpression of (pro)renin Receptor Induces Atrial Fibrillation in Mouse
Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, causing substantial cardiovascular morbidity and mortality. Renin-angiotensin system has been shown to be involved in the pathophysiology of AF. The (pro)renin receptor [(p)RR] is a new member of the renin-angiotensin system. However, the role of (p)RR in AF is still unknown.
Methods and Results: Circulating levels of (p)RR were determined by immunoradiometric assay in 22 patients with AF and 22 healthy controls. The plasma levels of (p)RR are increased 3.6-fold in atrial fibrillation patients (P≤0.0001), indicating the relationship between (p)RR and AF. To investigate the role of (p)RR in the regulation of cardiac arrhythmia, we generated transgenic mouse lines with overexpression of human (p)RR specifically in the heart. Electrocardiograms from (p)RR transgenic mice showed abnormal atrial electrophysiological properties since the age of 18 days. This atrial flutter with 3:1 to 4:1 atrioventricular conduction spontaneously converted to atrial fibrillation at the age of 6 months. The (p)RR transgenic mice have a high incidence of sudden death. Magnetic resonance imaging and histochemistry assessments showed normal ventricular size and function. In contrast, the atria of the transgenic mice demonstrate significantly dilation and fibrosis. Moreover, in the atria of the transgenic mice, SERCA gene decreased 38% (P≤0.05) and HCN4 increased 3 folds (P≤0.001), suggesting that (p)RR overexpression induced atrial fibrillation may be associated with the alternation of gene expression that regulate cardiac pace-making.
Conclusion: (p)RR promotes atrial structural remodeling and electrical remodeling in vivo. The (p)RR could be important gene involved in the pathological development of AF.
Key words: (pro)renin receptor [(p)RR]; atrial fibrillation (AF); transgenic mouse; heart; electrocardiogram
- © 2013 by American Heart Association, Inc.