Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arterial dysfunction and disease affect a majority of women during their life time. Ovarian hormones inhibit the development of atherosclerosis and play an integral role in the maintenance of normal arterial function. Estrogens act in the liver to improve and maintain lipid profiles and also act in the walls of arteries and in cardiac myocytes to maintain function and prevent disease. Death from cardiovascular disease is reduced in women receiving estrogen replacement therapy (ERT). Ten-year follow-up studies of women with advanced coronary artery disease (CAD) show a marked reduction in fatalities among the women receiving estrogens compared with untreated women. Sublingual estradiol-17 beta compared with placebo results in improved exercise tolerance and reduced ischemia during exercise in women with CAD. Estradiol-17 beta infused into the coronary arteries in women with CAD leads to improved arterial function. Estrogen deficiency has been reported in women with angina pectoris who have normal coronary arteries, and these women respond to estrogen treatment. HRT implies the use of ERT with the addition of a progestin. Progestins oppose the actions of estrogens. Counter-effects of lipid metabolism appear to be minimal with progestins currently in use. Oppositional effects of progestins on hemodynamic actions of estrogens may be significant, as progestins appear to induce vasoconstriction of estrogenized vessels.
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PMID:Cardiovascular disease in women: implications of hormone replacement therapy. 882 4

Estrogen deficiency is a risk factor for osteoporosis and coronary artery disease. Osteoporosis can be evaluated by measuring bone mineral density (BMD). Coronary atherosclerotic burden can be evaluated by measuring coronary calcium using electron beam computed tomography (EBT) of the heart. We compared coronary calcium scores in 45 asymptomatic postmenopausal women with normal and low BMD. BMD of the lumbar spine and proximal femur was measured by dual X-ray absorptiometry (DXA), and coronary calcium was measured quantitatively by EBT. Women were divided into control, osteopenia, and osteoporosis groups based on the T score of the lumbar spine. Women were similar in age, years since menopause, height, weight, and body mass index (BMI). BMD +/- SD (g/cm2) of L1-L4 was 0.96 +/- 0.11, 0.83 +/- 0.03, and 0.73 +/- 0.05, in control, osteopenia, and osteoporosis group, respectively. The total coronary calcium score +/- SD (relative units) was 41.9 +/- 83.1, 115.1 +/- 181.9, and 221.7 +/- 355.4 for control, osteopenia, and osteoporosis group, respectively; the score was significantly higher in the osteoporosis than in the control group. This study provides initial data suggesting that women with osteoporosis may have a higher risk of developing coronary atherosclerosis.
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PMID:Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women. 950 53

Estrogen deficiency, hyperinsulinemia, type II diabetes, atherosclerosis, and a past history of elevated blood pressure may be associated with increased risk of Alzheimer's disease (AD). Common to all of these risk factors is a diminished capacity of vascular endothelium to generate nitric oxide (NO). Vascular NO has the potential to enhance the membrane polarization of cerebral neurons by increasing the open probability of calcium-activated potassium channels; this may protect neurons from the excessive calcium influx, potentiated by beta-amyloid peptides that is thought to mediate neuronal damage in AD. The possibility that NO/cyclic guanosine 3', 5'-phosphate (cGMP) may modulate the synthesis or processing of the amyloid precursor protein, also merits evaluation. Practical measures for promoting vascular NO production may include increased intakes of arginine, potassium, antioxidants, and fish-oil, as well as lifestyle measures that typically lower elevated blood pressure; potential benefits of chromium, glucosamine, and silicon should also be explored. In hypertensives, angiotensin-converting enzyme (ACE) inhibitors and sodium restriction may favorably influence endothelial function. Fish-oil should have the additional benefit of antagonizing the contribution of interleukin-1 to AD pathogenesis. Ancillary anti-excitotoxic measures such as magnesium, taurine, phenytoin, and vasodilators targeting ATP-dependent potassium (KATP) channels, may likewise reduce AD risk. Most of the nutritional measures suggested here would in any case be recommendable for preservation of vascular health.
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PMID:Vascular nitric oxide may lessen Alzheimer's risk. 1005 65

Recent developments have advanced our knowledge of the role of estrogen in the male. Studies of the mutations in CYP19, the gene encoding aromatase, in six females and two males and a mutant estrogen receptor alpha in a man are described. These observations provide illuminating new insights into the critical role of estrogen in the male (as well as female) in the pubertal growth spurt and skeletal maturation, and in the importance of estrogen sufficiency in the accrual and maintenance of bone mass. The weight of evidence supports an effect of androgens on the latter processes, but this effect has not been quantitated. There is a discordance in the estrogen-deficient male between skeletal growth and skeletal maturation and the accrual of bone mass and density. Estrogen synthesis by the testis is limited before puberty, and estrogen deficiency does not affect the age of pubertal onset. Estrogen deficiency in men leads to hypergonadotropism, macroorchidism, and increased testosterone levels. Estrogen lack has a significant effect on carbohydrate and lipid metabolism, and estrogen resistance was associated with evidence of premature coronary atherosclerosis in a man. These observations have highlighted the role of extraglandular estrogen synthesis and intracrine and paracrine actions. In the human, in contrast to nonprimate vertebrates, aromatase deficiency and estrogen resistance (alpha) does not seem to affect gender identity or psychosexual development. The clinical repercussions of mutations in CYP19 on the fetal-placental unit have highlighted the major role of placental aromatase in the protection of the female fetus from androgen excess, thus preventing androgen-induced pseudohermaphrodism and virilization of the mother. These features are compared with the virilization that occurs in utero in the female spotted hyena. The novel features of the aromatase deficiency syndrome in the affected female--in the fetus, during childhood, and at puberty--are discussed, including virilization at puberty and development of polycystic ovaries. The severity of the syndrome correlates with the severity of impairment of aromatase formation in expression systems. Finally, the structural consequences of missense mutations in CYP19 are described in accordance with a model of the structure of human aromatase.
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PMID:Estrogen: consequences and implications of human mutations in synthesis and action. 1129 27

Due to the improving life expectancy of women spend third of their active life after the menopause. Estrogen deficiency can be caused by both natural and artificial menopause. The lack of estrogen can directly worsen the quality of life and epidemiological evidence suggests association with development of certain diseased states. Hormone replacement with natural estrogens has been proven to be successful for various indications: it reduces the menopausal vasomotor and psychological symptoms thus improving quality of life. It can also be used to prevent harmful effects of estrogen deficiency in various organs. Literature review supports the role of estrogen in atherosclerosis and osteoporosis prevention. Further evidence required establishing the role of estrogens in secondary prevention of coronary artery disease. Also needs to be explained why the beneficial effects of estrogen therapy in osteoporosis seem to disappear soon after cessation of therapy. Currently the relative risk increase of breast cancer during long-term hormone replacement therapy cannot be exactly measured. Nevertheless, substantial reduction of mortality in estrogen receptor positive breast cancer can also be seen with women on hormone replacement as compared to controls. Some data support the negative correlation of residual but still detectable, endogen estrogen and atherosclerosis and similarly to osteoporosis. The same residual estrogen levels seem to correlate positively with breast cancer. The recognition (and further acceptance) of the role of the residual estrogens might have influence on the indication, choice and dosage of preparation and duration of hormone replacement therapy. Overall evidence is in favor of the need medical attention for menopause: which ranges from preventive screening to long term hormone replacement therapy. The decision to treat requires the risks and benefits taken into consideration. This highly specialized care is provided in menopause clinics in Hungary. New oestrogen like agents are being developed like the selective estrogen receptor modulators, the tibolone and the phyto-estrogens. They provide tissue-specific effect acting as estrogen agonistics, sustaining the beneficial preventive and therapeutic effects of the estrogens, but in the breast and endometrial tissue they behave like estrogen antagonists avoiding the side effects of the current used oestrogens. They might play a significant role in the treatment of menopause in the future.
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PMID:[Menopause and hormone replacement therapy]. 1074 Nov 67

Estrogen deficiency is the major determinant of bone loss, not only in the first years postmenopause, but also throughout the entire life and in the elderly. Major progress in the knowledge of cellular actions of estrogens has been made leading to a better understanding of the underlying mechanisms of different estrogen-deficiency related diseases such as osteoporosis, atherosclerosis and also maybe cerebral aging. Estrogen replacement therapy remains the first choice treatment in the prevention of postmenopausal osteoporosis, but the continuous aging process of the female population raises the question of a better strategy of action in a more efficient prevention of hip fractures. Moreover, the potential gynecological effects of estrogens are likely to limit their indications or long-term use. The development of new compounds, called SERMs (selective estrogen receptor modulators), with both agonist and antagonist estrogen actions, in particular with no negative effects on the uterus and the breast opens new therapeutical insights into the prevention of postmenopausal osteoporosis.
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PMID:[Estrogens and selective estrogen receptor modulators in the treatment of osteoporosis]. 1110 29

The activity of several components of the vascular system appears to be diurnally regulated. Endothelial cell activation, leukocyte and platelet interactions and lipoprotein metabolism have all been shown to vary with time of day, but whether these variations are due to the endogenous circadian clock, exogenous factors, such as the light-dark cycle, or an interaction between the two remains to be determined. Endothelium-dependent vasodilation also varies diurnally. This rhythmicity is lost in individuals with established coronary disease has been shown to occur in the early stages of atherosclerosis. The incidence of coronary events appears to be higher in the early hours of the morning, this may be related to heightened activity of the autonomic nervous system at this time. Higher circulating levels of catecholamines in the morning are associated with increased vascular tone, affecting circulating blood volume and blood pressure. Time dependent variations may be of particular significance for individuals with disrupted circadian rhythms, including rotating shift workers, transmeridian travellers and blind individuals with no light perception. Variations in endothelial function are observed during the menstrual cycle, varying with circulating oestrogen levels. Oestrogen deficiency in postmenopausal women may contribute to endothelial dysfunction, together with other modifiable risk factors. The absolute risk of coronary disease is greater for men than for pre-menopausal women. Following the menopause gender differences in coronary risk are thought to diminish, although this remains controversial. This review focuses on the influence of both endogenous biological rhythms and environmental factors on the function and health of the human vascular system.
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PMID:Biological rhythms, endothelial health and cardiovascular disease. 1255 52

Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzyme activity and expression. The vasoprotective effects of estrogens may be related to antioxidative properties. Therefore, effects of 17beta-estradiol on production of reactive oxygen species and radical scavenging enzymes were investigated. 17beta-estradiol diminished angiotensin II-induced free radical production in vascular smooth muscle cells (DCF fluorescence laser microscopy). 17beta-estradiol time- and concentration-dependently upregulated manganese (MnSOD) and extracellular superoxide dismutase (ecSOD) expression (Northern and Western blotting) and enzyme activity (photometric assay). Nuclear run-on assays demonstrated that 17beta-estradiol increases MnSOD and ecSOD transcription rate. Half-life of MnSOD mRNA was not influenced, whereas ecSOD mRNA was stabilized by estrogen. Copper-zinc SOD, glutathione-peroxidase, and catalase were not affected by estrogen. Estrogen deficiency in ovariectomized mice induced a downregulation of ecSOD and MnSOD expression, which was associated with increased production of vascular free radicals and prevented by estrogen replacement or treatment with PEG-SOD. In humans, increased estrogen levels led to enhanced ecSOD and MnSOD expression in circulating monocytes. Estrogen acts antioxidative at least to some extent via stimulation of MnSOD and ecSOD expression and activity, which may contribute to its vasoprotective effects.
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PMID:Modulation of antioxidant enzyme expression and function by estrogen. 1281 84

Oxidative stress plays an important role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzymes. Estrogens exert antioxidative effects in the vasculature; however, cotreatment with progesterone may abrogate the vasoprotective effects of estrogen. Therefore, the effects of progesterone on the production of reactive oxygen species (ROS) and expression and function of antioxidant and oxidant enzymes were investigated in cultured vascular smooth muscle cells (VSMCs) and vascular tissue of mice. Progesterone time- and concentration-dependently downregulated extracellular superoxide dismutase (ecSOD) and manganese superoxide dismutase (MnSOD) expression and enzyme activity and reversed 17beta-estradiol-induced overexpression of ecSOD and MnSOD in VSMCs. Nuclear run-on assays revealed that progesterone decreases MnSOD and ecSOD transcription rates. Consequently, progesterone increased ROS release in VSMCs that was prevented by concomitant treatment with 17beta-estradiol. Estrogen deficiency in ovariectomized mice was associated with an increase in vascular superoxide release and NADPH oxidase activity. Estrogen replacement prevented this increase, whereas progesterone substitution enhanced ROS production and NADPH oxidase activity. The modulation of superoxide release coincided with decreased expression of ecSOD and MnSOD and upregulation of the p22phox and p67phox subunits of the NADPH oxidase complex in progesterone-treated animals. Furthermore, administration of progesterone to ovariectomized mice treated with 17beta-estradiol abrogated the antioxidative effects of estrogen. Progesterone antagonizes the vasoprotective effects of estrogen on ecSOD and MnSOD expression and increases NADPH oxidase activity. These findings may in part explain why hormone replacement therapy with estrogen plus progesterone displayed no beneficial effect on cardiovascular event rates in the prospective clinical trials.
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PMID:Progesterone antagonizes the vasoprotective effect of estrogen on antioxidant enzyme expression and function. 1619 79

Estrogen deficiency has been considered the seminal mechanism of osteoporosis in both women and men, but epidemiological evidence in humans and recent mechanistic studies in rodents indicate that aging and the associated increase in reactive oxygen species (ROS) are the proximal culprits. ROS greatly influence the generation and survival of osteoclasts, osteoblasts, and osteocytes. Moreover, oxidative defense by the FoxO transcription factors is indispensable for skeletal homeostasis at any age. Loss of estrogens or androgens decreases defense against oxidative stress in bone, and this accounts for the increased bone resorption associated with the acute loss of these hormones. ROS-activated FoxOs in early mesenchymal progenitors also divert ss-catenin away from Wnt signaling, leading to decreased osteoblastogenesis. This latter mechanism may be implicated in the pathogenesis of type 1 and 2 diabetes and ROS-mediated adverse effects of diabetes on bone formation. Attenuation of Wnt signaling by the activation of peroxisome proliferator-activated receptor gamma by ligands generated from lipid oxidation also contributes to the age-dependent decrease in bone formation, suggesting a mechanistic explanation for the link between atherosclerosis and osteoporosis. Additionally, increased glucocorticoid production and sensitivity with advancing age decrease skeletal hydration and thereby increase skeletal fragility by attenuating the volume of the bone vasculature and interstitial fluid. This emerging evidence provides a paradigm shift from the "estrogen-centric" account of the pathogenesis of involutional osteoporosis to one in which age-related mechanisms intrinsic to bone and oxidative stress are protagonists and age-related changes in other organs and tissues, such as ovaries, accentuate them.
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PMID:From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. 2005 26


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