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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several studies have provided evidence for a direct effect of 17beta-estradiol on vessel wall via interaction with the constitutively expressed nitric oxide synthase (NOS) by endothelium. The aim of the present study was to investigate the effect of 17beta-estradiol on inducible NOS (NOS II) in primary culture of smooth muscle cells (SMC) from rat aorta. We here prove that 17beta-estradiol decreases the content and activity of NOS II in SMC. This effect appears to be the consequence of ER activation, because: 1) ER alpha and ER beta are expressed in rat aorta SMC grown in culture; 2) low concentrations of hormone modulate NOS II activity; 3) the specific ER alpha antagonist ICI182,780 completely blocks 17beta-estradiol effect. On the other hand, progesterone is deprived of any effect on NOS II content or activity, proving the specificity of 17beta-estradiol effect. In addition, we show that 17beta-estradiol can counteract the increase in NOS II activity following cytokine treatment. The observation could indicate a novel mechanism for the protective effects exerted by these hormones in cardiovascular diseases and atherosclerosis in particular.
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PMID:17Beta-estradiol decreases nitric oxide synthase II synthesis in vascular smooth muscle cells. 1021 48

Studies on the effect of oestrogen on the circulatory apparatus have shown changes in vascular reactivity and structural alterations of blood vessels that participate in vascular growth and remodelling, whether physiological or pathological (atherosclerosis, ischaemia, restenosis). Direct vascular effects of oestradiol are mediated by functional steroid receptors, ER alpha and ER beta. ER alpha is predominantly found in arterial smooth muscle cells. During the menstrual cycle and pregnancy, endometrial vascular growth is required to allow embryo implantation and the development of the blood supply for fetal growth; oestradiol, in association with progesterone, promotes the growth of endometrial arteries, via ER and unknown mechanisms which probably involve the production of growth factors; oestradiol also induces endometrial angiogenesis, via the production of vascular endothelial growth factor (VEGF) by epithelial cells and fibroblasts. Oestradiol inhibits the proliferation of smooth muscle cells in the arterial wall (except in the genital tract), explaining in part the protective role of oestrogen against restenosis and chronic graft rejection. Further studies are required to determine the molecular mechanisms of these actions and the respective role of ER alpha and ER beta.
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PMID:[Effect of estrogens on vascular proliferation]. 1050 Apr 47

Although estrogen-dependent effects on the vasculature were first observed more than a century ago, many of the mechanisms by which estrogens interact with the vascular wall have been identified only in the past 15 years. Estrogens bind to vascular estrogen receptors (ER), including the ER alpha, the novel ER beta as well as to membrane-bound receptors. Estrogens have direct effects in human coronary and internal mammary arteries by inducing rapid, endothelium-independent relaxation, enhancement of endothelial function and inhibition of vasoconstriction by vasoactive agonists. Furthermore, estrogens contribute to vascular homeostasis through modulation of gene expression, changes in membrane potentials, as well as expression and function of receptors. In addition, estrogens interfere with the activity of vasoactive peptides and vascular enzymes and act as natural antioxidants. Some of these effects have also been observed for phyto-estrogens, which are important dietary components in Asian countries. In the vasculature, the sum of these actions of estrogens results in vasodilatation and inhibition of vascular cell growth. Accordingly, estrogens have been shown to improve vascular function of animals and humans and to inhibit the response to injury after balloon angioplasty and the progression of atherosclerosis. Prospective clinical studies are ongoing to determine whether replacement therapy with estrogen or derivatives provides an alternative to lower cardiovascular mortality in postmenopausal women.
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PMID:Vascular effects of estrogens: rapid actions, novel mechanisms, and potential therapeutic implications. 1067 98

Cardiovascular diseases are the major causes of illness and death in women. Premenopausal women are relatively protected from coronary artery disease and atherosclerosis as compared to postmenopausal women, and this protection is attributed to the effects of the female sex hormone (estrogen). The vasculature, like the reproductive tissues, bone, liver, and brain, is now recognized as an important site of estrogen's action. Although estrogen's beneficial effects on the cardiovascular system are well described in many studies, the molecular basis of estrogen protective mechanisms are still quite vague. Both genomic mechanisms, mediated primarily through estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta), and non-genomic mechanisms, through nitric oxide (NO), of estrogen action are controversial and do not entirely explain the effects of estrogen on vascular preservation during conditions of oxidative stress. Until recently, the atheroprotective effects of estrogen were attributed principally to its effects on serum lipid concentrations and cholesterol levels. However, two recent reports that estrogen therapy has no effect on the progression of coronary atherosclerosis in women with established disease, despite the favorable changes in LDL and cholesterol levels, leads to questions about the lipid/cholesterol mechanism of estrogen-mediated effects on atherosclerosis. Alternatively, the high level of homocysteine, found to correlate with accelerated cardiovascular disease and identified as an independent risk factor for atherosclerosis, was recently described to be diminished by estrogen. Protection against disturbed sulfhydryl metabolism and higher homocysteine level could be the missing link in understanding how exactly estrogen affects vascular cells metabolism and responses to oxidative stress. This review focuses on estrogen/homocysteine interactions and their relevance to the cardiovascular system.
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PMID:Estrogen and homocysteine. 1186 Oct 28

Estrogen has direct and indirect effects on the cardiovascular system that are mediated by the estrogen receptors ER-alpha and ER-beta. The direct effects of estrogen occur through rapid nongenomic and longer-term genomic pathways. The rapid effects of estrogen are mediated by ERs and result in the activation of endothelial nitric oxide synthase, leading to arterial vasodilation. Longer-term effects involve changes in gene and protein expression, modulating the response to injury and atherosclerosis. Estrogen also indirectly influences serum lipoprotein and triglyceride profiles, and the expression of coagulant and fibrinolytic proteins. Advanced atherosclerosis and certain progestins, however, may attenuate some of the protective effects of estrogen.
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PMID:Protective effects of estrogen on the cardiovascular system. 1208 97

As early as the 1950s, animal studies showed that exogenous estrogen could inhibit coronary atherosclerosis. Since then, additional animal studies have helped to further elucidate the cardiovascular effects of hormone replacement therapy and the importance of the timing of therapy initiation. Although estrogen's cardioprotective effects in women are believed to be related, in part, to its effects on lipoprotein levels, studies in monkeys show that estrogen acutely modulates the vasomotor response of atherosclerotic coronary arteries without significantly changing lipoprotein levels, indicating a direct vascular effect. Studies in both rats and primates indicate that some of the antiatherogenic effects of estrogens may be counteracted by specific progestins. Models using a nonselective estrogen receptor (ER) antagonist (ICI 182,780) indicate that the antiatherogenic effects of 17 beta-estradiol are mediated via ERs. Recent studies with ER knockout mice indicate that ER-alpha and ER-beta mediate the protective effects of estrogen on the vasculature. Additional studies are ongoing to define the mechanisms through which specific estrogens and progestins affect cardiovascular function and to clarify the impact of the timing of initiation of therapy on the atherosclerotic process.
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PMID:Animal models of the cardiovascular effects of exogenous hormones. 1210 36

The effects of estrogen on the female reproductive system are well known. In contrast, comparatively recent research has demonstrated that estrogen also exerts specific effects on the cardiovascular system--particularly the vasculature. This review summarizes some of the current ideas of how estrogen regulates and modulates vascular function, and focuses primarily on potential mechanisms of estrogen-induced vasodilation. Although many studies indicate estrogen exerts beneficial effects on the circulatory system, the overall conclusions from clinical studies remain somewhat equivocal. In contrast, it is clear that estrogen reduces atherosclerosis by reducing low-density lipoproteins (LDL) and inflammatory processes in the vasculature, and may also act as an antioxidant; however, these effects account for only a portion of the total cardiovascular benefit of estrogen. Estrogen is also a vasodilator and hypotensive agent, and can induce vascular relaxation by stimulating release of endothelium-derived vasodilatory substances (e.g., nitric oxide [NO]) or by acting directly on the vascular smooth muscle (VSM). Recent evidence indicates that calcium and potassium channels in VSM cells play an important role in mediating estrogen-induced relaxation of many vascular beds, but elucidating the signal transduction mechanisms coupling estrogen receptor (ER alpha and/or ER beta) activation to generation of second messengers and effector mechanisms remains an area of intense study. Not surprisingly, it is becoming apparent that the molecular basis of estrogen's influence on vascular function is multifactorial. A better understanding of these signaling mechanisms should lead to the development of powerful therapeutic agents which can maximize the many beneficial effects of estrogen action, while helping minimize the harmful (and sometimes lethal) side effects.
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PMID:Estrogen and vascular function. 1237 53

Epigenetic changes marked by DNA methylation have been proposed to play a role in age-related disease. We investigated DNA methylation changes in cardiovascular atherosclerotic tissues and in-vitro vascular senescence in the promoter of estrogen receptor beta gene, which has essential roles in vascular function. Coronary atherosclerotic tissues showed higher methylation levels (28.7%) than normal appearing arterial (6.7%-10.1%) and venous tissues (18.2%). In comparing estrogen receptor beta methylation between plaque and non-plaque regions in ascending aorta, common carotid artery, and femoral artery of two patients, the plaque lesions showed consistently higher methylation levels than non-plaque regions. Passage-dependent increased estrogen receptor beta methylation was observed in three of six human aortic endothelial or smooth muscle cell lines cultured in-vitro to vascular senescence. Estrogen receptor beta expression in these vascular cell lines was significantly activated by DNA-methyltransferase inhibition. This activity was augmented by histone deacetylase inhibition. These findings provide evidence of epigenetic dysregulation of estrogen receptor beta in atherosclerosis and vascular aging. We suggest that focal epigenetic changes in estrogen receptor beta contribute to the development of atherosclerosis and vascular aging.
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PMID:Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence. 1711 88

Inflammation is recognized as a key component in a number of diseases, including rheumatoid arthritis, inflammatory bowel disease and atherosclerosis. Although well known for their classic effects on the reproductive tract and action by means of estrogen response elements in gene promoters, estrogens are also known to possess anti-inflammatory activity. This was originally highlighted with the observation that pregnancy ameliorates symptoms of rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Furthermore, the antagonistic cross talk between nuclear factor kappaB and estrogen receptor signaling pathways has been well documented. Recently, novel estrogen receptor ligands, pathway-selective ligands and estrogen receptor beta-selective ligands have been identified which demonstrate potent anti-inflammatory activity; these ligands are being analyzed for their therapeutic potential in pathogenic inflammation.
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PMID:Estrogen receptor ligands in the control of pathogenic inflammation. 1711 88

Male cynomolgus macaques (n=91) consumed an isoflavone (IF)-free, atherogenic control diet containing casein/lactalbumin for 5 months, then were randomized to three groups: control (n=30) continued on the control diet; low IF (n=30) received a mixture of unmodified and IF-depleted soy protein isolate (SPI) (0.94 mg IF/g protein, approximating a human intake of 75 mg/day); high IF (n=31) received unmodified SPI (1.88 mg IF/g protein, approximating a human intake of 150 mg/day) for 31 months. Iliac and carotid artery atherosclerosis, and arterial and hepatic mRNA transcripts related to inflammation and estrogen receptors (ER) were measured. Trend analysis identified a significant inverse relationship between dietary IF content and plaque area in the iliac (p<0.05) but not carotid arteries (p>0.13). No significant effect of diet on inflammatory gene or estrogen receptor expression was observed. Plaque area was positively correlated with the mRNA transcript levels for arterial MCP-1, ICAM-1, and the macrophage marker CD68 (all r>0.25, p<0.03), and negatively correlated with ER alpha and ER beta (all r<-0.23, p<0.03). Coronary artery plaque area appeared to be more closely associated with gene expression patterns of the iliac arteries than the carotid arteries. The data suggests benefits of dietary soy on atherosclerotic plaque development in males may be mediated through inflammation-independent pathways. The negative associations of arterial ER alpha expression with atherosclerosis lend support to a mechanistic role for estrogen receptors in atherosclerosis susceptibility which merits further study.
Atherosclerosis 2008 Jan
PMID:Effects of dietary soy protein on iliac and carotid artery atherosclerosis and gene expression in male monkeys. 1736 95


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