title: Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction.
abstract: 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).
  
  
  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 microL/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 microL/g in TG and 1.63+/-0.41 microL/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.
authors.affiliation: Department of Medicine and the Cardiovascular Research Center, University of Virginia Health System, Charlottesville 22908, USA.
authors.forename: Zequan
authors.initials: Z
authors.lastname: Yang
authors.forename: Christina M
authors.initials: CM
authors.lastname: Bove
authors.forename: Brent A
authors.initials: BA
authors.lastname: French
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Epstein
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Berr
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DiMaria
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Gibson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Carey
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Kramer
mesh_terms: D000818:Animals; D006439:Hemodynamics; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin