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

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 (AT1-R and AT2-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) microm, 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; AT1-R 0.7+/-0.06 (A), 0.9+/-0.07 (B), and 0.3+/-0.04 (C), P<0.01; AT2-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.