Female mice lacking estrogen receptor beta display prolonged ventricular repolarization and reduced ventricular automaticity after myocardial infarction.
BACKGROUND
Major gender-based differences in the incidence of ventricular tachyarrhythmia after myocardial infarction have been shown in humans. Although the underlying mechanisms are unclear, earlier studies suggest that estrogen receptor-mediated effects play a major role in this process.


RESULTS
We examined the effect of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) on the electrophysiological phenotype in female mice with and without chronic anterior myocardial infarction. There was no significant difference in overall mortality, infarct size, and parameters of left ventricular remodeling when we compared infarcted ERalpha-deficient and ERbeta-deficient mice with infarcted wild-type animals. In the 12-hour telemetric ECG recording 6 weeks after myocardial infarction, surface ECG parameters did not show significant differences in comparisons of ERalpha-deficient mice versus wild-type controls, infarcted versus noninfarcted ERalpha-deficient mice, and infarcted ERalpha-deficient versus infarcted wild-type mice. However, infarcted ERbeta-deficient versus noninfarcted ERbeta-deficient mice showed a significant prolongation of the QT (61+/-6 versus 48+/-8 ms; P<0.05) and QTc intervals (61+/-7 versus 51+/-9 ms; P<0.05) and the JT (42+/-6 versus 31+/-4 ms; P<0.05) and JTc intervals (42+/-7 versus 33+/-4 ms; P<0.05). Furthermore, infarcted ERbeta-deficient versus infarcted wild-type mice showed a significant prolongation of the QT (61+/-6 versus 53+/-8 ms; P<0.05) and QTc intervals (61+/-7 versus 53+/-7 ms; P<0.05) and the JT (42+/-6 versus 31+/-5 ms; P<0.05) and JTc intervals (42+/-7 versus 31+/-5 ms; P<0.05), accompanied by a significant decrease of ventricular premature beats (7+/-21/h versus 71+/-110/h; P<0.05). Finally, real-time polymerase chain reaction-based quantitative analysis of mRNA levels showed a significantly lower expression of Kv4.3 (coding for I(to)) in ERbeta-deficient mice (P<0.05).


CONCLUSIONS
Estrogen receptor beta deficiency results in prolonged ventricular repolarization and decreased ventricular automaticity in female mice with chronic myocardial infarction.
Korte
Thomas
T
Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany. korte.thomas@mh-hannover.de
Fuchs
Martin
M
Arkudas
Andreas
A
Geertz
Sebastian
S
Meyer
Rainer
R
Gardiwal
Ajmal
A
Klein
Gunnar
G
Niehaus
Michael
M
Krust
Andrée
A
Chambon
Pierre
P
Drexler
Helmut
H
Fink
Klaus
K
Grohé
Christian
C
D000818:Animals; D004562:Electrocardiography; D047628:Estrogen Receptor alpha / Q000172:deficiency; D047629:Estrogen Receptor beta / Q000172:deficiency*; D005260:Female; D008133:Long QT Syndrome / Q000209:etiology; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051672:Shal Potassium Channels / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000209:etiology*; D018879:Ventricular Premature Complexes / Q000209:etiology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D051672:Shal Potassium Channels