Left Ventricular Reverse Remodeling After Surgical Therapy for Aortic Stenosis: Correlation to Renin-Angiotensin System Gene Expression

Abstract

Background Surgical therapy for aortic stenosis leads to reverse remodeling, with normalization of left ventricular hypertrophy (LVH). The aim of this study was to examine Renin-Angiotensin system (RAS) gene expression in this setting. Methods Growing sheep (n=44) underwent supracoronary aortic banding for controlled induction of LVH at the age of 6 to 8 months (A=baseline). Surgical revision to completely release the pressure gradient was performed 8.3±1 months later (B). The animals were sacrificed after another 10.1±2 months (C). Along with hemodynamic measurements, subtractive hybridization and competitive polymerase chain reaction were applied to quantify mRNA expression for angiotensin-converting enzyme (ACE) and angiotensin receptors 1 and 2 (AT 1 -R and AT 2 -R). Results Left ventricular mass index was 82±21 g (A), 150±33 g (B), and 78±18 g (C), P <0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter was 11.3±0.8 (A), 15.9±1.2 (B), and 11.4±1 (C) μm, P <0.01. Gene expression was as follows: ACE 0.8±0.05 (A), 1.3±0.08 (B), and 0.9±0.06 (C), P <0.01; AT 1 -R 0.7±0.06 (A), 0.9±0.07 (B), and 0.3±0.04 (C), P <0.01; AT 2 -R 0.5±0.05 (A), 0.2±0.04 (B), and 0.5±0.05 (C), P <0.01. Conclusion LVH in aortic stenosis coincides with significant alterations of the RAS. Surgical therapy leads to reverse remodeling, which is paralleled by regression of RAS gene expression.