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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen is believed to protect postmenopausal women from coronary vascular disease, in part by increasing production of nitric oxide (NO). In this study, we investigated the possibility that transcriptional activation of inducible NO synthase (iNOS) is responsible for a component of the estrogen-induced increase in coronary blood flow. Twenty-two ewes were instrumented with Doppler flow probes on their left circumflex coronary and pulmonary arteries. Nine ewes received 17beta-estradiol (1 microg/kg), and the coronary vascular response was followed for 16 h. Estradiol significantly increased coronary blood flow by 22 +/- 4% over baseline and the peak response occurred at 2 h (P < 0.01). To examine the effect of estrogen on NOS expression in the ovine coronary artery, 17 noninstrumented animals were killed 2 h after administration of estradiol or vehicle. Coronary arteries were analyzed for ovine iNOS and endothelial NOS (eNOS) expression by semiquantitative RT-PCR. PCR primers were based on partial cDNA clones for ovine eNOS and iNOS isolated as part of this study. The expression of iNOS was significantly increased (27-fold) by the administration of estradiol, whereas the expression of eNOS was much weaker (2-fold). To confirm these effects in vivo, additional instrumented animals received either the estrogen receptor (ER) antagonist ICI-182,780 (n = 5), the iNOS antagonist dexamethasone (n = 5), or pyrrolidine dithiocarbamic acid, an inhibitor of nuclear factor-kappaB (n = 5). All three antagonists inhibited estrogen-induced increases in coronary blood flow and increases in cardiac output by over 85%. These results strongly support the hypothesis that 17beta-estradiol increases coronary blood flow in the unanesthetized nonpregnant ewe via an ER-dependent mechanism that results in an increase in both eNOS and iNOS expression.
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PMID:Estrogen increases iNOS expression in the ovine coronary artery. 1218 Nov 48

The effect of quinestrol compound on fat metabolism in 206 women who took quinestrol compound for 5-13 years and in 159 controls was studied. The blood concentration of CL, TG, and FFA was examined in each of the cases and controls. The value of every indicator in fat metabolism of the cases who took quinestrol compound for 5 years was markedly higher than in the controls (p0.001 in cholesterol, p0.05 in B-LP, p0.01 in HDL). The effect of oral contraceptives (OCs) consisting of estrogen and progesterone on fat metabolism were dependent on the type and dosage of steroids. Estrogen was associated with an increase of CL, HDL-CL, and a decrease of LDL-CL, while progesterone has little effect on the level of blood fat. The elevated CL and TG level is believed to be associated with cardio vascular disease, while a higher level of HDL is protective against the disease. Therefore, precautions should be taken with longterm use of estrogen, especially with large doses as substantially higher levels of TG and FFA were found in longterm rather than in shortterm users, while the difference in HDl was not as big. It was suggested that clients with a high level of blood fat, high blood pressure, and liver disease should choose alternative contraceptive methods and users of OCs should switch to other methods after 5 years.
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PMID:[Effect of compound quinestrol on fat metabolism]. 1231 89

Estrogen agonists/antagonists, when administered orally, exert a range of effects on hepatic function, some of which are potentially protective. These effects include reduced synthesis of IGF-I and apolipoprotein(a), and increased synthesis of IGFBP-1--shifts which arguably could decrease risk for vascular disease and certain cancers. These effects are diametrically opposite to those of growth hormone (GH), which boosts hepatic production of IGF-I and apolipoprotein(a), while suppressing that of IGFBP-1. Thus, a parsimonious explanation of these phenomena is that oral estrogen blunts the efficiency of GH signaling in the liver. Oral androgenic progestins may have the reverse effect. It may be of particular value to determine whether certain estrogen agonists/antagonists can exert relatively 'hepatospecific' activity when administered orally--thus enabling down-regulation of systemic IGF-I activity and of lipoprotein(a), without however inducing a significant increase in systemic estrogen activity. Preliminary evidence suggests that flax lignans and perhaps other phytoestrogens may have potential in this regard.
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PMID:Estrogen agonists/antagonists may down-regulate growth hormone signaling in hepatocytes--an explanation for their impact on IGF-I, IGFBP-1, and lipoprotein(a). 1294 1

Bench research suggests that postmenopausal hormonal therapy is associated with beneficial effects on the brain and vascular system. Observational data suggest that postmenopausal hormone replacement therapy is associated with a 25% to 50% lower rate of cardiovascular disease; however, observational data for hormonal therapy is associated with the potential for significant biases. Clinical trial data are needed. There are 3 major clinical trials that inform us about stroke and postmenopausal hormone replacement therapy. Two trials focused on secondary prevention: the Heart and Estrogen/progesterone Replacement Study (HERS) and the Women's Estrogen for Stroke Trial (WEST). One examined primary prevention: the Women's Health Initiative (WHI). All indicate that postmenopausal hormone therapy is not effective for reducing the risk of a recurrent stroke or death among women with established vascular disease or for prevention of a first stroke. Similar results exist for cardiovascular disease. The results of these trials are now reflected in national guidelines. Hormone therapy should not be initiated to prevent vascular disease among postmenopausal women. As a result of these trials, the portion of postmenopausal women using hormone replacement therapy in the United States has fallen by more than half over the past decade.
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PMID:Hormone replacement therapy and stroke: clinical trials review. 1545 43

Estrogen is known to induce rapid vasodilatory response in isolated arteries. Because estrogen is a nonselective receptor agonist, the involvement of estrogen receptor (ER) subtypes in acute estrogenic responses has remained elusive. Acute administration of the selective ERalpha agonist 4,4',4''-(4-propyl-[(1)H]pyrazole-1,3,5-triyl) tris-phenol (PPT) to precontracted aortic rings from intact female rats dose-dependently induced an ER-dependent vascular relaxation fully overlapping to that induced by 17beta-estradiol. By contrast, the selective ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) had no acute effect on vasomotion. This short-term vasorelaxant action of PPT was abolished by the NO synthase inhibitor N(omega)-nitro-l-arginine methyl ester and by endothelium removal. In aortic tissues from ovariectomized (OVX) rats, however, neither 17beta-estradiol nor PPT induced acute vascular relaxation. The effect of PPT was restored in preparations from estrogen-replaced OVX rats, whereas DPN remained ineffective even after estrogen replacement. PPT acted through an ER-dependent mechanism, as shown by impaired response in the presence of the anti-estrogen ICI 182,780 (7alpha,17beta-[9[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol). Accordingly, isolated rat aortic endothelial cells expressed both ERalpha and ERbeta. These data show that selective ERalpha but not ERbeta agonists reproduced the acute vasodilation of estrogen via a receptor-mediated pathway in the aorta from intact as well as 17beta-estradiol-replaced OVX rats. This beneficial effect was undetectable in tissues from OVX rats. Selective pharmacological targeting of ER subtypes may thus represent a novel and promising approach in the treatment of vascular disease.
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PMID:The acute estrogenic dilation of rat aorta is mediated solely by selective estrogen receptor-alpha agonists and is abolished by estrogen deprivation. 1572 4

Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of vascular disease. Clinical studies have shown that postmenopausal women have higher serum TNF-alpha levels; however, whether this increase in TNF-alpha is associated with vascular dysfunction is unknown. We investigated whether estrogen deficiency is associated with increased serum TNF-alpha levels and tested the effects of in vivo TNF-alpha inhibition on vascular reactivity. Aged (12 to 15 months) Sprague-Dawley rats were ovariectomized and treated with placebo, estrogen, or a TNF-alpha inhibitor (Etanercept; 0.3 mg/kg) for 4 weeks. Serum TNF-alpha was determined by a bioassay, and vascular function was evaluated in the myograph system. Estrogen-deficient animals had higher serum levels of TNF-alpha compared with either estrogen-replaced animals or animals treated with Etanercept. Moreover, in estrogen-deficient rats, TNF-alpha inhibition reduced the constriction of mesenteric arteries to phenylephrine, increased the modulation of this vasoconstriction by the NO synthase inhibitor nitro-l-arginine methyl ester, and decreased the modulation by a superoxide scavenger (Mn(III)tetrakis(4-benzoic acid) porphyrin chloride). Furthermore, endothelium-dependent relaxation was also enhanced by TNF-alpha antagonism. Additionally, vascular expression of endothelial NO synthase was increased in animals treated with Etanercept, whereas the expression of NAD(P)H oxidase gp91phox and p22phox subunits was decreased. These data show that estrogen-deficient female rats have higher bioactive serum TNF-alpha levels compared with estrogen-replaced animals. Moreover, a decrease in serum bioactive TNF-alpha by a soluble TNF-alpha receptor (Etanercept) results in increased modulation of vascular function by NO. These observations suggest that TNF-alpha could be a mediator of vascular dysfunction associated with estrogen deficiency.
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PMID:Chronic tumor necrosis factor-alpha inhibition enhances NO modulation of vascular function in estrogen-deficient rats. 1591 37

Mitochondrial dysfunction has been implicated as a cause of age-related disorders, and the mitochondrial theory of aging links aging, exercise, and diet. Endothelial dysfunction is a key paradigm for vascular disease and aging, and there is considerable evidence that exercise and dietary restriction protect against cardiovascular disease. Recent studies demonstrate that estrogen receptors are present in mitochondria and that estrogen promotes mitochondrial efficiency and decreases oxidative stress in the cerebral vasculature. Chronic estrogen treatment increases mitochondrial capacity for oxidative phosphorylation while decreasing production of reactive oxygen species. The effectiveness of estrogen against age-related cardiovascular disorders, including stroke, may thus arise in part from hormonal effects on mitochondrial function. Estrogen-mediated mitochondrial efficiency may also be a contributing factor to the longer lifespan of women.
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PMID:Estrogen and mitochondria: a new paradigm for vascular protection? 1650 48

The regulation of the estrogenic responses may be influenced by the proteins that associate with estrogen receptors (ERs) rather than solely with the receptors themselves. ERbeta is expressed in blood vessels and may play an important role in vascular disease. We hypothesized that specific proteins interact with ERbeta to modulate its response to estrogens. By means of a yeast two hybrid screen, we discovered that NM23-H2, a multi-faceted protein associates specifically with ERbeta. NM23-H2 and ERbeta consistently co-localize in a variety of human tissues (e.g. breast tissue), whereas ERalpha and NM23-H2 did not co-localize. Estrogen response element-mediated transcription increased by 97% when NM23-H2 and ERbeta were over-expressed in MCF-7 cells (p< or =0.001). Moreover, there was a synergistic effect of NM23-H2 over-expression with estrogen treatment on the reduction of MCF-7 cell migration (p< or =0.001). These results suggest that NM23-H2 associates with ERbeta and is capable of modulating estrogen-induced gene transcription, as well as cell migration. Hence, NM23-H2 may play an important role in modulating the response to endogenous and exogenous estrogens, perhaps even within the context of vascular disease.
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PMID:Discovery of NM23-H2 as an estrogen receptor beta-associated protein: role in estrogen-induced gene transcription and cell migration. 1796 37

Although estrogen has been clinically available for more than six decades, women have been confused by different opinions regarding the risks and benefits of menopausal hormone therapy (HT), estrogen therapy (ET), and estrogen-progestin therapy (EPT). The publication of randomized controlled trials (RCTs), notably, the Heart and Estrogen/progestin Replacement Study (HERS) and Women's Health Initiative (WHI), has intensified the risk vs. benefit controversy. Millions of women are treated with HT for relief of menopausal symptoms, including vasomotor flushes and sweats, for which estrogen is uniquely and highly effective. Others may continue longer-term treatment in the hope that HT will help to prevent chronic disease. The preservation of bone mass with continuing estrogen therapy and reduction of subsequent risk of fracture is well established. Observational studies of the metabolic and vascular effects of estrogens have suggested a potential benefit in reducing the risk of vascular disease, but recently published randomized controlled trials demonstrated no evidence of benefit in women with established vascular disease or in apparently healthy women. The increased risks of breast cancer and thromboembolic disease have been confirmed in these trials, with evidence of increased risk of stroke. The absolute incidence of an adverse event is low, and the risk of stroke in an individual woman in a single year is very small, but with long-term use, the risks are cumulative over time. The risk-benefit balance needs to be individualized for each woman.
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PMID:[Hormone replacement therapy in menopause]. 2483 May 94

Gender medicine has been a major focus of research in recent years. The present review focuses on gender differences in the epidemiology of the most frequent ocular diseases that have been found to be associated with impaired ocular blood flow, such as age-related macular degeneration, glaucoma and diabetic retinopathy. Data have accumulated indicating that hormones have an important role in these diseases, since there are major differences in the prevalence and incidence between men and pre- and post-menopausal women. Whether this is related to vascular factors is, however, not entirely clear. Interestingly, the current knowledge about differences in ocular vascular parameters between men and women is sparse. Although little data is available, estrogen, progesterone and testosterone are most likely important regulators of blood flow in the retina and choroid, because they are key regulators of vascular tone in other organs. Estrogen seems to play a protective role since it decreases vascular resistance in large ocular vessels. Some studies indicate that hormone therapy is beneficial for ocular vascular disease in post-menopausal women. This evidence is, however, not sufficient to give any recommendation. Generally, remarkably few data are available on the role of sex hormones on ocular blood flow regulation, a topic that requires more attention in the future.
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PMID:Gender differences in ocular blood flow. 2489 19


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