Effects of 17beta-estradiol on cardiac apoptosis in ovariectomized rats.
OBJECTIVE
Cardiac apoptosis was found in ovariectomized rats without ischemia. Limited information regarding the protective effects of 17beta-estradiol (E2) on cardiac Fas-dependent and mitochondria-dependent apoptotic pathways after post-menopause or bilateral oophorectomy in women was available.


METHODS
Forty-eight female Wistar rats at 6-7 months of age were divided into sham-operated group (Sham, n = 16) and bilateral ovariectomized group (n = 32). After 4 weeks of operation, rats in ovariectomized group were injected intraperitoneally with either saline (OVX, n = 16) or 10 microg/kg/day 17beta-estradiol (E2) for 10 weeks (OVX-E2, n = 16). The excised hearts were measured by Hematoxylin-eosin staining, DAPI staining, positive TUNEL assays, and Western Blotting.


RESULTS
17beta-estradiol (E2) decreased OVX-induced cardiac widely dispersed TUNEL-positive apoptotic cells. 17beta-estradiol (E2) decreased OVX-induced TNF-alpha, Fas ligand (Fas L), Fas death receptors (Fas), Fas-associated death domain (FADD), activated caspase 8, and activated caspase 3 (Fas pathways). 17beta-estradiol (E2) decreased OVX-induced proapoptotic t-Bid, Bax, Bax-to-Bcl2 ratio, Bax-to-BclXL ratio, activated caspase 9, and activated caspase 3 as well as increased anti-apoptotic Bcl2 and Bcl-XL relative to OVX (mitochondria pathway).


CONCLUSIONS
Our findings suggest that chronic 17beta-estradiol (E2) treatment can prevent ovariectomy-induced cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in rat models. The findings may provide one of possible mechenisms of 17beta-estradiol (E2) for potentially preventing cardiac apoptosis after bilateral ovariectomy or menopause.
Liou
Cher-Ming
CM
Department of Anesthesiology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Yang
Ai-Lun
AL
Kuo
Chia-Hua
CH
Tin
Hua
H
Huang
Chih-Yang
CY
Lee
Shin-Da
SD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage*; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D010052:Ovariectomy / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
D053222:Fas Ligand Protein; D019014:fas Receptor; D004958:Estradiol