A comparative study of efficacy of tibolone and simvastatin on atherosclerosis in ovariectomized cholesterol-fed rabbits.
BACKGROUND
After menopause women are more susceptible to coronary heart disease due to increased risk of atherosclerosis. Tibolone (Livial) is an innovative synthetic steroid analogue for the treatment of postmenopausal climacteric symptoms including atherosclerosis, but the mechanisms of its effect are still unclear. The present study investigated the effect of tibolone and simvastatin on atherosclerosis and the expression of both estrogen receptor A (ERA) and LDL receptor (LDLR) mRNA in ovariectomized cholesterol-fed rabbits.


METHODS
Fifty New Zealand white rabbits were included for the study. Of them, 40 underwent bilateral ovariectomy and the other 10 were sham-operated. The sham-operated group only received atherogenic diet (group SC) and the ovariectomized rabbits were divided into 4 groups of 10 each, with group N received normal diet, group C received atherogenic diet, group T received atherogenic diet and tibolone (2.5 mg/day) and group SI received atherogenic diet and simvastatin (20 mg/day). After 12 weeks of the treatments, the animals were euthanized and the extent of thoracic aortic atherosclerosis was measured morphologically and the level of ERA and LDLR mRNA in heart and liver was determined by real-time RT-PCR.


RESULTS
The extent of atherosclerosis in the thoracic aorta was 0.75+/-0.24 for group C, 0.56+/-0.27 for group SC, almost 0 for group N, 0.10+/-0.02 for group T and 0.09 +/-0.08 for group SI (P<0.01; groups T versus C, T versus SC, SI versus C, SI versus SC). The relative copies of ERA at group C, SC, N, T and SI were 0.29, 0.53, 0.46, 0.85 and 0.30, respectively in heart and 0.32, 0.51, 0.49, 0.68 and 0.30, respectively in liver; the relative copies of LDLR at group C, SC, N, T and SI were 0.22, 0.24, 0.33, 0.27 and 0.23, respectively in heart and 0.68, 0.93, 1.52, 1.27 and 0.88, respectively in liver.


CONCLUSIONS
Both tibolone and simvastatin prevented the atherosclerosis in ovariectomized cholesterol-fed rabbits and this effect was associated with up-regulation of ERA and LDLR expression by tibolone but not by simvastatin.
Cui
Yali
Y
College of Veterinary Medicine, China Agriculture University, Beijing 100094, China.
Zhao
Deming
D
Liu
Hongxiang
H
Ning
Zhangyong
Z
Yang
Jianmin
J
Qing
Xiuhui
X
Yu
Shumin
S
Wu
Changde
C
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D002784:Cholesterol / Q000008:administration & dosage; D017931:DNA Primers; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006937:Hypercholesterolemia; D009652:Norpregnenes / Q000008:administration & dosage / Q000627:therapeutic use*; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011960:Receptors, Estrogen / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D017931:DNA Primers; D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011973:Receptors, LDL; D002784:Cholesterol; D019821:Simvastatin; C027385:tibolone