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(Circulation. 2002;106:106.)
© 2002 American Heart Association, Inc.

Basic Science Reports

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

Zequan Yang, MD, PhD^*; Christina M. Bove, MD^*; Brent A. French, PhD; Frederick H. Epstein, PhD; Stuart S. Berr, PhD; Joseph M. DiMaria, BA; Jennifer J. Gibson, MS; Robert M. Carey, MD; Christopher M. Kramer, MD

From the Departments of Medicine (C.M.B., R.M.C., C.M.K.), Radiology (B.A.F., F.H.E., S.S.B., J.M.D., C.M.K.), Biomedical Engineering (Z.Y., B.A.F., F.H.E., S.S.B.), and Health Evaluation Sciences (J.J.G.) and the Cardiovascular Research Center, University of Virginia Health System, Charlottesville.

Correspondence to Christopher M. Kramer, MD, University of Virginia Health System, Departments of Medicine and Radiology, Lee St, Box 800170, Charlottesville, VA 22908. E-mail ckramer{at}virginia.edu

Background— The role of the angiotensin II type 2 receptor (AT₂-R) in left ventricular (LV) remodeling may depend on the underlying stimulus. We hypothesized that cardiac AT₂-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 AT₂-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 AT₂-R overexpression improves LV systolic function at baseline and preserves function during post-MI remodeling.

Key Words: remodeling • myocardial infarction • magnetic resonance imaging • angiotensin • receptors

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