Angiotensin II Type 2 Receptor Overexpression Preserves Left Ventricular Function After Myocardial Infarction

Abstract

Background — The role of the angiotensin II type 2 receptor (AT 2 -R) in left ventricular (LV) remodeling may depend on the underlying stimulus. We hypothesized that cardiac AT 2 -R overexpression in transgenic (TG) mice would attenuate remodeling after myocardial infarction (MI). Methods and Results — Ten wild-type (WT) C57BL/6 mice and 12 TG mice that overexpress the AT 2 -R in the heart were studied by cardiac MRI at baseline and days 1, 7, and 28 post-MI induced by 1 hour of occlusion of the LAD followed by reperfusion. Short-axis imaging from apex to base was used to determine LV mass index, end-diastolic and end-systolic volume indices (EDVI, ESVI), regional wall thickness and thickening, and ejection fraction (EF). Gadolinium-DTPA was infused 20 minutes before day 1 imaging to assess infarct size. At baseline, heart rate, blood pressure, LV mass index, and EDVI were similar between groups. Baseline ESVI was lower (0.20±0.07 versus 0.45±0.15 μL/g, P <0.001) and EF higher (82.3±4.9% versus 67.7±5.3%, P <0.001) in TG than WT. Infarct size was similar (36.6±7.2% in WT, 34.0±7.8% in TG, P =NS). When controlled for baseline differences, ESVI was significantly less and EF significantly higher at all time points in TG versus WT. At day 28, ESVI was 1.05±0.32 μL/g in TG and 1.63±0.41 μL/g in WT, P <0.03, and EF was 47.3±5.8% versus 34.1±9.2%, P <0.003, respectively. Regional wall thickness and thickening were greater in TG both at baseline and at day 28. At day 28, blood pressure and LV dP/dt were higher in TG. Conclusions — Cardiac AT 2 -R overexpression improves LV systolic function at baseline and preserves function during post-MI remodeling.