17-beta-estradiol increases cardiac remodeling and mortality in mice with myocardial infarction.
OBJECTIVE
This study was designed to examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after myocardial infarction (MI) in mice.


BACKGROUND
Observational and clinical studies suggest that the cardiovascular effects of hormone replacement therapy can differ depending on the patient population studied. No prospective studies have examined the effect of estrogen on outcomes following MI. We now examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after MI in mice.


METHODS
Myocardial infarction was induced by left coronary artery ligation in ovariectomized female mice treated with 17-beta-estradiol (E2) or placebo. At either one day or six weeks after MI, hemodynamic function was assessed, animals were euthanized, and infarct size was determined.


RESULTS
17-beta-estradiol-treated mice had smaller infarcts than placebo-treated animals both one day (18% decrease; p < 0.01), and six weeks (14% decrease; p < 0.05) following MI. E2 reduced cardiomyocyte apoptosis as assessed by the terminal deoxynucleotidyl transferase uridine nucleotide end-labeling method (50% reduction, p < 0.05) and caspase 3 activation (33% reduction, p < 0.05). Despite having smaller infarcts, however, left ventricular mass increased more in the E2-treated animals (16% greater; p < 0.01). Left ventricular weight was positively correlated with infarct size in the estrogen-treated animals (R2 = 0.79, p = 0.0001). 17-beta-estradiol treatment also significantly increased mortality in the infarcted animals (relative risk of death = 2.4; 95% confidence interval 1.2 to 5.3).


CONCLUSIONS
Estrogen replacement therapy reduces infarct size and cardiomyocyte apoptosis in mice. However, estrogen increased post-MI ventricular remodeling and mortality. Further studies will be necessary to elucidate the mechanisms underlying the complex effects of estrogen observed in the present study.
van Eickels
Martin
M
Medizinsche Poliklinik II, University of Bonn, Bonn, Germany.
Patten
Richard D
RD
Aronovitz
Mark J
MJ
Alsheikh-Ali
Alawi
A
Gostyla
Kim
K
Celestin
Flore
F
Grohe
Christian
C
Mendelsohn
Michael E
ME
Karas
Richard H
RH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004452:Echocardiography; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects; D016019:Survival Analysis; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology*; D016387:Women's Health
D004958:Estradiol