title: 17 Beta-estradiol differentially affects left ventricular and cardiomyocyte hypertrophy following myocardial infarction and pressure overload.
abstract: BACKGROUND
  We have shown previously that 17beta-estradiol (E2) increases left ventricular (LV) and cardiomyocyte hypertrophy after myocardial infarction (MI). However, E2 decreases hypertrophy in pressure overload models. We hypothesized that the effect of estrogen on cardiac hypertrophy was dependent on the type of hypertrophic stimulus.
  
  
  RESULTS
  Ovariectomized wild-type female mice (n = 192) were given vehicle or E2 treatment followed by coronary ligation (MI), transverse aortic constriction (TAC), or sham operation. Signaling pathway activation was studied at 3, 24, and 48 hours, whereas echocardiography and hemodynamic studies were performed at 14 days. MI induced early but transient activation of p38 and p42/44 MAPK pathways, whereas TAC induced sustained activation of both pathways. E2 had no effect on these pathways, but increased Stat3 activation after MI while decreasing Stat3 activation after TAC. MI caused LV dilation and decreased fractional shortening (FS) that were unaltered by E2. TAC caused LV dilation, reduced FS, and increased LV mass, but in this model, E2 improved these parameters. After MI, E2 led to increases in myocyte cross-sectional area, atrial natriuretic peptide (ANP) and beta-myosin heavy chain (MHC) gene expression, but E2 diminished TAC-induced increases ANP and beta-MHC gene expression.
  
  
  CONCLUSIONS
  These data demonstrate that the effects of E2 on LV and myocyte remodeling depend on the nature of the hypertrophic stimulus. The opposing influence of E2 on hypertrophy in these models may, in part, result from differential effects of E2 on Stat3 activation. Further work will be necessary to explore this and other potential mechanisms by which estrogen affects hypertrophy in these models.
authors.affiliation: Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Patten
authors.forename: Isaac
authors.initials: I
authors.lastname: Pourati
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Aronovitz
authors.forename: Alawi
authors.initials: A
authors.lastname: Alsheikh-Ali
authors.forename: Sarah
authors.initials: S
authors.lastname: Eder
authors.forename: Thomas
authors.initials: T
authors.lastname: Force
authors.forename: Michael E
authors.initials: ME
authors.lastname: Mendelsohn
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D017548:Echocardiography, Transesophageal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010052:Ovariectomy; D011336:Probability; D016016:Proportional Hazards Models; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D004958:Estradiol