Effects of estrogens on lipoprotein metabolism and cardiovascular disease in women

Knopp, Robert H.; Zhu, Xuming; Bonet, Bartolomé

doi:10.1016/0021-9150(94)05379-w

Cited by 128 publications

(61 citation statements)

References 20 publications

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“…Estrogen is known to play a role in the delayed expression of coronary heart disease in women, and its supplement to postmenopausal women was reported to reduce the incidence of coronary heart disease. 39,40 The precise mechanism(s) by which estrogen produces this bene®t is unknown, although its effects on blood pressure, carbohydrate, lipid metabolism, 41 and endothelial cell functions have been suggested. 42 On the other hand, a hyperandrogenic state re¯ected by high testosterone, high free testosterone and low sex hormone-binding globulin levels was reported to be associated with abdominal obesity in women.…”

Section: Discussionmentioning

confidence: 99%

Preperitoneal fat thickness determined by ultrasonography is correlated with coronary stenosis and lipid disorders in non-obese male subjects

et al. 2000

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OBJECTIVE: To investigate the relationship between preperitoneal fat thickness (PFT) determined by ultrasonography and the risk of coronary arterial disease, 130 non-obese patients with ischemic heart disease (77 men and 53 women) were examined. RESULTS: There was a positive correlation between PFT and coronary artery stenosis score (r 0.212, P`0.05). After dividing the patients by gender, the correlation was recognized only in men (r 0.246, P`0.05). Also, PFT was positively correlated to serum total cholesterol (r 0.259, P`0.01), triglyceride (r 0.205, P`0.05) and low density lipoprotein (LDL)-cholesterol (r 0.205, P`0.05), and negatively correlated to serum high density lipoprotein (HDL)-cholesterol (r 7 0.261, P`0.01). Again, these correlations were found only in men, not in women. CONCLUSION: PFT shows good correlations with coronary artery stenosis score and dislipidemia, and may lead to the development of coronary artery disease in non-obese male subjects.

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Section: Discussionmentioning

confidence: 99%

Preperitoneal fat thickness determined by ultrasonography is correlated with coronary stenosis and lipid disorders in non-obese male subjects

et al. 2000

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“…These trends suggest that estrogen plays a central role in the sex differences in CVD (Waldron 1983;Vaccarino et al 2010). Some studies that have examined the indirect effects of female hormones have found that estrogen has positive effects on lipoprotein profiles by decreasing total cholesterol and LDL cholesterol levels and increasing HDL cholesterol levels (Knopp et al 1994;Miller et al 1995). The direct effects of estrogen have been mainly attributed to two estrogen receptor subtypes, ERa and ERb, which are located in vascular endothelial and myocardial cells; as well as to a recently discovered third membrane-bound estrogen receptor, the G-protein-coupled estrogen receptor (GPR30) (Babiker et al 2002;Mendelsohn and Karas 2005;Prossnitz and Maggiolini 2009).…”

Section: Effects Of Estrogenmentioning

confidence: 99%

Sex Differences in Health and Survival

Oksuzyan

Gumà

Doblhammer

2018

A Demographic Perspective on Gender, Family and Health in Europe

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“…This led to the hypothesis that the TG-lowering action of ACOL may depend on nutritional status. Estrogen favors hypertriglyceridemia through an increase in hepatic VLDL secretion (20). Whether ACOL affects TG appearance in or clearance from the circulation is unknown.…”

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confidence: 99%

Hypolipidemic action of the SERM acolbifene is associated with decreased liver MTP and increased SR-BI and LDL receptors

Lemieux

Gélinas

Lalonde

et al. 2005

Journal of Lipid Research

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This study aimed to identify the mechanisms of the hypolipidemic action of the selective estrogen receptor modulator (SERM) acolbifene (ACOL). Four weeks of treatment with ACOL reduced fasting and postprandial plasma triglycerides (TGs), an effect associated with lower VLDL-TG secretion rate ( ؊ 25%), and decreased mRNA of microsomal triglyceride transfer protein (MTP; ؊ 29%). ACOL increased liver TG concentration ( ؉ 100%) and amplified the feeding-induced increase in the master lipogenic regulators sterol-regulatory element binding protein-1a (SREBP-1a) and SREBP-1c. ACOL decreased total, HDL, and non-HDL cholesterol (CHOL) by 50%. SREBP-2 mRNA and HMG-CoA reductase activity were minimally affected by ACOL. However, in the fasted state, liver concentration of scavenger receptor class B type I (SR-BI) protein, but not mRNA, was 3-fold higher in ACOL-treated than in control animals and correlated with plasma HDL-CHOL levels ( r ‫؍‬ 0.80, P Ͻ 0.002). Liver LDL receptor (LDLR) protein, but not mRNA, was increased 2-fold by ACOL, independently of the nutritional status. This study demonstrates that ACOL possesses the unique ability among SERMs to reduce VLDL-TG secretion, likely by reducing MTP expression, and strongly suggests that the robust hypocholesterolemic action of ACOL is related to increased removal of CHOL from the circulation as a consequence of enhanced liver SR-BI and LDLR abundance. The concerns raised by the Women's Health Initiative Study regarding the health risks/benefits of hormone replacement therapy in postmenopausal women (1-3) strengthen the interest in evaluating the metabolic properties of other steroids as well as selective estrogen receptor modulators (SERMs) to improve the quality of life of this population. The estrogen antagonist acolbifene (ACOL; EM-652.HCl) is a SERM that was developed for the prevention and treatment of estrogen-sensitive cancers (4, 5). The compound behaves as a highly potent and pure antiestrogen in human breast and uterine cancer cells in vitro as well as in vivo in nude mice (4, 5). ACOL binds selectively to both the ␣ and ␤ types of estrogen receptors (6). Despite its pure antiestrogenic activity in the mammary gland and endometrium, ACOL can be classified as a SERM based on some estrogen-like properties, such as prevention of bone loss, decreasing plasma lipids (7-9), and reduction in body weight (mostly fat) gain (9, 10) in animal models. Therefore, ACOL shares actions on energy balance and lipemia with other steroids, such as various anticarcinogenic agents (11-15) and dehydroepiandrosterone (16)(17)(18)(19).One of the most striking actions of ACOL in rodent models is its robust hypolipidemic action. In rats, a triglyceride (TG)-lowering action has been reported in freely fed rats treated for 9 months with the ACOL prodrug EM-800 (8). Also, ACOL was found not to increase triglyceridemia, compared with estradiol treatment, in ovariectomized rats (10). Therefore, ACOL may beneficially affect triglyceridemia, at least under some conditions, an effect ...

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Effects of estrogens on lipoprotein metabolism and cardiovascular disease in women

Cited by 128 publications

References 20 publications

Preperitoneal fat thickness determined by ultrasonography is correlated with coronary stenosis and lipid disorders in non-obese male subjects

Preperitoneal fat thickness determined by ultrasonography is correlated with coronary stenosis and lipid disorders in non-obese male subjects

Sex Differences in Health and Survival

Hypolipidemic action of the SERM acolbifene is associated with decreased liver MTP and increased SR-BI and LDL receptors

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