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In vivo analysis of cardiac cell death with age and estrogen deficiency in the female rat: protective effects of acute estrogen receptor‐α activation
Author(s) -
Eldred Stephanie V.,
Ball Richard W.,
Hunter J. Craig,
Korzick Donna H.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1060.5
Subject(s) - apoptosis , medicine , estrogen receptor , dna laddering , programmed cell death , estrogen , endocrinology , cardioprotection , in vivo , myocardial infarction , andrology , biology , biochemistry , microbiology and biotechnology , cancer , breast cancer , dna fragmentation
Background Myocardial infarction is a leading cause of death in U.S. women. Both necrotic and apoptotic cell death contribute to cardiac ischemia/reperfusion (I/R) injury, however the relative roles of each in I/R injury with age‐associated estrogen (E 2 ) deficiency is unknown. Whether rapid activation of estrogen receptor α (ERα) influences cell death type with aging is also unknown. Purpose To determine the effects of acute ERα activation on necrotic vs apoptotic cell death following I/R injury in aged, E 2 ‐deficient female rat hearts. Methods In vivo left coronary artery ligation (CAL; 55 min I, 2 to 6 hrs R) was performed on adult (6 mo; n=6) and aged (24 mo; n=12) F344 rats with ovaries intact or removed (OVX; aged only). The ERα agonist propylpyrazole triol (PPT; 5 μg/kg s.c.) or vehicle were administered 45 min prior to CAL. Area at risk was assessed using Evans Blue dye (0.8%), infarct analysis performed using 1% triphenyltetrazolium chloride staining, apoptosis using DNA laddering, and NF‐κB mRNA levels through real time PCR. Results PPT reduced infarct size by ~50% in aged and aged OVX. Reductions in NF‐κB mRNA following I/R were also reversed by PPT (p<0.05), suggesting an anti‐apoptotic effect. Conclusion Acute ERα activation confers cardioprotection in vivo by reducing both necrotic and apoptotic cell death in aged, E 2 ‐deficient rats following I/R injury. Supported by NHLBI RO1 HL091097