Cardiovascular risk in women: the impact of hormone replacement therapy and prospects for new therapeutic approaches

Jeanes, Helen L; Newby, David E.; Gray, Gillian A.

doi:10.1517/14656566.8.3.279

Cited by 21 publications

(12 citation statements)

References 80 publications

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“…Accordingly, estrogen, its receptor and its coregulatory proteins, has been implicated in the pathologies of a variety of diseases and cancers [13, 14, 15, 16]. Furthermore, these large pleiotropic effects are a serious complication in using hormone or hormone derivatives as potential therapeutics [17, 18, 19]. Technologies that increase specificity for estrogen activity or possibly target it to cells, tissues or independent genes, have tremendous applicability in therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and functional analysis of novel bivalent estrogens

et al. 2010

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The steroid hormone estrogen plays a critical role in female development and homeostasis. Estrogen mediates its effects through binding and activation of specific estrogen receptors alpha (ERα) and beta (ERβ), members of the steroid/nuclear receptor family of ligand-induced transcription factors. Due to their intimate roles in genomic and nongenomic signaling pathways, these hormones and their receptors have been also implicated in the pathologies of a variety of cancers and metabolic disorders, and have been the target of large therapeutic development efforts. The binding of estrogen to its respective receptors initiates a cascade of events that include receptor dimerization, nuclear localization, DNA binding and recruitment of co-regulatory protein complexes. In this manuscript, we investigate the potential for manipulating steroid receptor gene expression activity through the development of bivalent steroid hormones that are predicted to facilitate hormone receptor dimerization events. Data are presented for the development and testing of novel estrogen dimers, linked through their C-17 moiety, that can activate estrogen receptor alpha (ERα)-mediated transcription events with efficacy and potency equal to or greater than that of ERα’s cognate ligand, 17β-estradiol. These bivalent estrogen structures open the door to the development of a variety of steroid therapeutics that could dramatically impact future drug development in this area.

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Section: Introductionmentioning

confidence: 99%

Synthesis and functional analysis of novel bivalent estrogens

et al. 2010

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“…Although apoM is not present in all HDL particles, recent data have demonstrated a positive correlation between serum apoM levels and HDL cholesterol concentrations in man [9]. Wolfrum and his 4 colleagues, using apoM-deficient mice, demonstrated that apoM is important for preβ-HDL formation and cholesterol efflux from macrophages; thus, apoM-deficient HDL was markedly less efficient in facilitating cholesterol efflux from macrophages in vitro than normal HDL [10]. Moreover, over-expression of apoM in LDL-receptor knock-out mice protected against atherosclerosis when fed a high cholesterol diet [10], suggesting that apoM may play an important role in HDL metabolism and protect against atherosclerosis.…”

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confidence: 98%

“…In general, these effects of estrogen are considered beneficial from the atherogenic point of view. However, randomised, controlled trials of estrogen supplementation in postmenopausal women have failed to demonstrate a benefit of estrogens in the primary or secondary prevention of cardiovascular diseases (CVD), although estrogens might be effective if targeted at younger perimenopausal women [4].…”

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confidence: 99%

Estrogen upregulates hepatic apolipoprotein M expression via the estrogen receptor

Jiang¹,

Shi²,

Zhang³

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Apolipoprotein M (apoM) is present predominantly in high-density lipoprotein (HDL) in human plasma, thus possibly involved in the regulation of HDL metabolism and the process of atherosclerosis. Although estrogen replacement therapy increases serum levels of apoAI and HDL, it does not seem to reduce the cardiovascular risk in postmenopausal women. Therefore, we investigated the effects of estrogen on apoM expression in vitro and in vivo. HepG2 cells were incubated with different concentrations of estrogen with or without the estrogen receptor antagonist, fulvestrant, and apoM expression in the cells was determined. Hepatic apoM expression and serum levels of apoM were also determined in normal and in ovariectomized rats treated with either placebo or estradiol benzoate, using sham operated rats as controls. Estrogen significantly increased mRNA levels of apoM and apoAI in HepG2 cell cultures in a dose-and time-dependent manner; the upregulation of both apolipoproteins was fully abolished by addition of estrogen receptor antagonist. In normal rats, estrogen treatment led to an increase in plasma lipid levels including HDL cholesterol, a marked upregulation of apoM mRNA and a significant increase in serum levels of apoM. The same pattern of regulation was found in ovariectomized rats treated with estrogen. Thus, estrogen upregulates apoM expression both in vivo and in vitro by mechanism(s) involving the estrogen receptor.

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“…It is related to the symptoms and metabolic effects of sex steroid deficiency, as well as the emotional sequelae experienced by couples who have difficulty in conceiving a pregnancy [34]. In addition, POF is associated with risks of cardiovascular disease, osteoporosis, and psychiatric diseases [35–37]. Currently, there are no effective treatments for this disease.…”

Section: Discussionmentioning

confidence: 99%

Effects of Bushen Tianjing Recipe in a rat model of tripterygium glycoside-induced premature ovarian failure

Tan

Jiang

et al. 2017

Chin Med

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BackgroundBushen Tianjing Recipe (BTR) is a traditional Chinese herbal medicine that has been prescribed for premature ovarian failure (POF) for decades in China. Nevertheless, little is known regarding its underlying molecular mechanism. In the present study, we investigated the effects of BTR in a tripterygium glycoside (TG)-induced-POF rat model.MethodsThree doses of BTR were administered via intragastric gavage to adult female Sprague–Dawley (SD) rats with TG-induced POF. After 15 days of treatment, the estrous cycle was examined by vaginal smear analysis. Serum levels of estradiol, follicle-stimulating hormone, progesterone, and testosterone were measured by radioimmunoassay. Histological analysis and assessment of apoptosis were performed after hematoxylin and eosin staining of ovarian tissue sections. The expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), anti-apoptotic factor Bcl-2, and pro-apoptotic factors Bax and caspase 3 in ovaries of animals was examined by an immunohistochemistry process.ResultsBTR not only reverted an abnormal estrous cycle and decreased the ovary index in POF rats but also improved the abnormal secretion of reproductive hormones associated with POF. In addition, treatment with BTR can protect ovaries from TG-induced damage, induce intraovarian expression of VEGF and VEGFR2, and regulate intraovarian expression of apoptosis-related proteins.ConclusionsOur results show that BTR is effective in the treatment of TG-induced POF rats. Promotion of angiogenesis and anti-apoptosis are most likely to contribute to the effects of BTR against POF.Electronic supplementary materialThe online version of this article (doi:10.1186/s13020-017-0131-3) contains supplementary material, which is available to authorized users.

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Cardiovascular risk in women: the impact of hormone replacement therapy and prospects for new therapeutic approaches

Cited by 21 publications

References 80 publications

Synthesis and functional analysis of novel bivalent estrogens

Synthesis and functional analysis of novel bivalent estrogens

Estrogen upregulates hepatic apolipoprotein M expression via the estrogen receptor

Effects of Bushen Tianjing Recipe in a rat model of tripterygium glycoside-induced premature ovarian failure

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