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

Oral contraceptives (OC) have been shown to enhance the risk of atherosclerosis. In the present study we sought to determine which component of the OC (containing 0.067 mg estrogen and 0.667 mg of progestin) counts for alteration in lipids profile. Female rats were administered with 0.067 mg of 17 beta-estradiol and 0.667 mg of norethindron acetate/kg body weight. Estrogen treatment exhibited higher levels of lipids in the serum and tissues. LDL-cholesterol increased by three folds but HDL-cholesterol decreased significantly, while progestin group showed decreased levels of lipids and LDL cholesterol. Elevated hepatic cholesterogenesis was observed as indicated by increased activity of HMG-CoA reductase and elevated incorporation of labelled acetate into liver cholesterol in estrogen group. On the other hand, progestin treatment did not alter the activity of HMG-CoA reductase and the rate of incorporation of labelled acetate into hepatic cholesterol. Hepatic degradation of cholesterol to bile acids however, decreased with estrogen treatment. No considerable changes were observed in hepatic bile acid levels in progestin group. Release of lipoprotein into circulation increased but their clearance from the circulation decreased as revealed by the activity of lipoprotein lipase (LPL) of extrahepatic tissues in estrogen group. With progestin treatment, activity of LPL increased significantly in adipose tissue. Activity of hepatic malic enzyme and glucose 6-phosphate dehydrogenase enhanced considerably in estrogen group, while activities of these enzymes were depressed with progestin administration. Thus results indicate that estrogen component of oral pills counts for major changes in lipid and lipoprotein metabolism favouring the development of atherosclerosis.
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PMID:Influence of components of oral contraceptive on lipid metabolism. 864 14

Widespread application of proven primary and secondary preventive strategies for coronary heart disease would result in substantial savings of life and health care dollars. Proven strategies (excluding lipid therapy) include quitting smoking, treating hypertension, physical activity, aspirin therapy, and appropriate use of anticoagulants, beta blockers, and angiotensin-converting enzyme inhibitors in survivors of myocardial infarction. Estrogen replacement therapy is currently under clinical investigation. Avoidance of obesity and tight control of diabetes are prudent interventions as yet unproved by clinical trials. Unfortunately, preventive strategies are frequently underutilized. The greatest challenge for preventive cardiology is to put into practice what we already know to prevent the development and progression of atherosclerosis.
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PMID:Nonlipid primary and secondary prevention strategies for coronary heart disease. 872 3

A protective effect of estrogen is the most obvious reason for the substantial and consistent favored status of women vs. men with regard to coronary heart disease (CHD). This paper briefly reviews the history of studies of the estrogen-heart disease hypothesis, the reason why clinical trials of postmenopausal estrogen are necessary (despite the strength, consistency, and plausibility of the 'protection' seen in observational studies), and the status of the 'Postmenopausal Estrogen/Progestin Interventions' (PEPI) trial results and ongoing trials. The potential for nonhormonal primary prevention is emphasized.
Atherosclerosis 1995 Dec
PMID:Postmenopausal estrogen and heart disease. 882 60

The Atherosclerosis Risk in Communities Study investigators examined nearly 4000 postmenopausal women from 1987 through 1989 and 3 years later to determine changes in plasma lipids occurring with the starting or stopping of hormone replacement therapy. Women who started estrogen plus progestin therapy (n = 74) had decreases of 9.8 mg/dl in low-density lipoprotein (LDL) cholesterol and 5.8 mg/dl in apolipoprotein B and increases of 1.2 mg/dl in high-density lipoprotein (HDL) cholesterol (HDL change not significant), 13.5 mg/dl in apolipoprotein A-I, and 14.0 mg/dl in triglycerides. Women who started estrogen alone (n = 149) had similar changes, except for a much larger increase in HDL cholesterol (5.8 mg/dl), principally in HDL-2. Women who stopped hormone therapy (n = 138) had lipid changes opposite to those who started therapy, but smaller in magnitude. These results confirm those of the Postmenopausal Estrogen/Progestin Interventions Trial in a community-based longitudinal cohort: women initiating estrogen plus progestin therapy have decreases in LDL cholesterol, but the increase in HDL cholesterol is less than that for starting estrogen alone. In addition, the current study extends findings to apolipoproteins and HDL subfractions.
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PMID:Changes in plasma lipids and lipoproteins associated with starting or stopping postmenopausal hormone replacement therapy. Atherosclerosis Risk in Communities Study. 889 66

Estrogen provides beneficial effects on hyperlipidemia in climacteric and elderly women. In this study of 68 women (37 to 67 years old), hepatic triglyceride lipase (HTGL), lipoprotein lipase (LpL) serum lipids and apolipoproteins were analyzed to investigate the effects of estrogen replacement therapy (ERT). After menopause, LpL, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B increased. But ERT suppressed total cholesterol, LDL-cholesterol, apolipoprotein B, and especially apolipoprotein E in menopausal women. The mechanism was thought that ERT significantly suppressed HTGL, but LpL was not affected. Estrogen also increases hepatic LDL receptors and accelerates transfer of serum LDL-C (and TC). It was said that HTGL accelerates conversion of intermediate-density lipoprotein (IDL) to LDL. The suppression of HTGL by the ERT may decrease conversion of IDL to LDL and lower LDL-C (and TC). These estrogen's beneficial effects on lipids, may prevent the atherosclerosis. In addition, apolipoprotein E increases senile plaques in senile dementia-Alzheimer's type. The decrease in apolipoprotein E with ERT may be related to cognitive functions of elderly women.
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PMID:Effect of estrogen replacement therapy on hepatic triglyceride lipase, lipoprotein lipase and lipids including apolipoprotein E in climacteric and elderly women. 907 16

Estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women and inhibits progression of coronary artery atherosclerosis in monkeys. Tamoxifen is a nonsteroidal compound with mixed estrogen agonist and antagonist properties. Its antagonist activity is useful in chemotherapy of breast cancer and may have protective effects on plasma lipid concentrations, but its effects on atherogenesis have not been defined. The goal of this study was to examine the effect of tamoxifen on plasma lipids, arterial and hepatic LDL metabolism, and progression of coronary artery atherosclerosis in surgically postmenopausal female monkeys. Thirty-five monkeys were fed an atherogenic diet containing 1.3 mg.kg-1.d-1 tamoxifen (equivalent to the usual dose of 20 mg/d given to women). Thirty-one monkeys were fed the same atherogenic diet with no tamoxifen. Ten monkeys from each treatment group were fed the test diets for 12 weeks to examine the short-term effects of tamoxifen on arterial LDL metabolism. The rest of the monkeys were fed the test diets for 3 years to study the long-term effects of tamoxifen on development of atherosclerosis. In the short term, tamoxifen inhibited the rate of arterial accumulation of LDL degradation products overall (P = .03) and decreased hepatic cholesterol content (P = .003). In the long term, tamoxifen increased plasma concentrations of triglycerides (0.60 +/- 0.67 versus 0.23 +/- 0.02 mmol/L, P = .001) and reduced average LDL molecular weight (5.3 +/- 0.2 versus 4.8 +/- 0.1 g/mumol, P = 0.004) but had no effects on plasma total, LDL, or HDL cholesterol concentrations. Coronary artery atherosclerosis (intimal area, mean +/- SEM) was 0.25 +/- 0.06 mm2 in control monkeys and 0.12 +/- 0.03 mm2 in tamoxifen-treated monkeys (P = .057). We conclude that tamoxifen has antiatherogenic effects that may be modulated in part through direct effects on arterial LDL metabolism.
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PMID:Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys. 908 97

This study was designed to determine the effect of several hormone replacement therapies on LDL size, density, heterogeneity, and composition in surgically postmenopausal cynomolgus monkeys fed an atherogenic diet. Groups (n = 5 each) of ovariectomized cynomolgus monkeys were untreated (control), or treated with conjugated equine estrogens, medroxyprogesterone acetate (progesterone), combined estrogen-progesterone, or tamoxifen for 9 weeks. There were no differences among treatment groups in total plasma, LDL, or HDL cholesterol or triglyceride concentrations. Plasma LDL were isolated by ultracentrifugation and size exclusion chromatography and subfractionated by density gradient centrifugation for subsequent chemical analysis. Estrogen treatment was associated with significantly smaller (measured as LDL molecular weight, 3.9 +/- 0.2 g/mu mol) and denser plasma LDL (1.034 g/ml peak density) compared with control (4.5 +/- 0.1 g/mu mol; 1.030 g/ml peak density) or progesterone-treated animals (4.6 +/- 0.2; 1.029 g/ml peak density). LDL from the estrogen group were relatively enriched in protein and triglyceride and poor in cholesteryl ester and apolipoprotein F (apoE) compared to the control group. Triglyceride enrichment with estrogen treatment occurred predominantly in the lighter, larger LDL subfractions (d = 1.015-1.025 g/ml), which were reduced in concentration (26 +/- 10 mg cholesterol/dl) compared to control (61 +/- 19 mg/dl) or progesterone treated animals (67 +/- 16 mg/dl). Combined estrogen-progesterone or tamoxifen treatment resulted in changes in LDL that followed the same trend as those observed with estrogen treatment. We conclude that short-term estrogen treatment of ovariectomized cynomolgus monkeys results in changes in plasma LDL size, density, and composition while having no apparent effect on overall plasma lipid concentrations.
Atherosclerosis 1996 Apr 05
PMID:Effects of hormone replacement modalities on low density lipoprotein composition and distribution in ovariectomized cynomolgus monkeys. 912 96

The present study was performed to elucidate the mechanism underlying the anti-atherogenic action of estrogen. We investigated the effect of estrogen on intimal thickening of the rat femoral artery induced by cuff placement and further examined the effect of estrogen on migration and proliferation of vascular smooth muscle cells (VSMCs) in culture. Intimal thickening was significantly greater in males than in control females. Intimal thickening in females was increased to the level in males by ovariectomy. Estrogen replacement to ovariectomized rats reversed this effect. Proliferating cell nuclear antigen immunohistochemistry showed that in vivo proliferation of VSMCs contributed to the difference in intimal thickening. There was no difference in blood pressure and serum lipids, suggesting that estrogen directly acted on artery and inhibited intimal thickening. 17 beta-Estradiol (E2, 1-100 nmol/l) inhibited migration of cultured rat VSMCs, assayed using a microchemotaxis chamber, in a concentration-dependent manner. E2 (0.01-100 nmol/l), but not progesterone or testosterone, also inhibited [3H]thymidine incorporation in rat VSMCs in a concentration-dependent manner. Indomethacin, NG-monomethyl-L-arginine and methylene blue did not influence the inhibitory action of E2 on [3H]thymidine incorporation, suggesting that prostanoids and nitric oxide are not involved in the action of E2. E2 did not provoke VSMC injury, as measured by the release of incorporated [3H]2-deoxy-D-glucose. These results suggest that the inhibition of migration and proliferation of VSMCs contributes to the inhibitory effect of estrogen on intimal thickening.
Atherosclerosis 1997 Apr
PMID:Estrogen inhibits cuff-induced intimal thickening of rat femoral artery: effects on migration and proliferation of vascular smooth muscle cells. 912 42

Estrogen replacement therapy (ERT) decreases the progression of coronary artery atherosclerosis in monkeys. Dietary soy protein also retards the progression of atherosclerosis relative to animal proteins such as casein. Soy protein contains weakly estrogenic compounds called isoflavones or phytoestrogens that may be responsible for the cardioprotective effects. This study was designed as a 2 x 2 factorial to determine the magnitude of soy protein's effects on cardiovascular risk factors relative to casein and lactalbumin, with or without estradiol treatment. Ovariectomized female monkeys were randomized to four treatment groups based on past dietary cholesterol consumption, their origin, and past reproductive history, and studied for 7 months. The animals were divided into (1) a group fed casein and lactalbumin as the protein source (n = 14), (2) a group fed casein and lactalbumin as the protein source plus 17 beta-estradiol (E2) (n = 13), (3) a group fed soybean protein isolate as the protein source (n = 11), and (4) a group fed soybean protein isolate as the protein source plus E2 (n = 10). Soy protein compared with casein consumption resulted in a significant improvement in plasma lipid and lipoprotein concentrations, a significant improvement in insulin sensitivity and glucose effectiveness as determined by minimal-model analyses, and a decrease in arterial lipid peroxidation. E2-treated monkeys had a significant reduction in fasting insulin levels and insulin to glucose ratios, total body weight, and amounts of abdominal fat, and had smaller low-density lipoprotein (LDL) particles. In addition, E2 treatment resulted in a significant reduction (P = .001) in aortic cholesteryl ester content. A similar trend (P = .14) was found for soy protein compared with casein. There also was a significant interaction (P = .02) with soy and E2, such that animals consuming soy protein +E2 had the least arterial cholesteryl ester content. These results suggest that both ERT and dietary soybean protein have beneficial effects on cardiovascular risk factors. Interestingly, the two treatments affected different risk factors and together resulted in the greatest reduction in arterial cholesterol content. Further studies are needed to determine the active component of the soy protein and to assess its long-term effects on the cardiovascular system and other organ systems (such as the bones and reproductive system).
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PMID:Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys. 918 8

While estrogen is known to prevent the development of atherosclerosis, the mechanism is not completely understood. We investigated the effects of superoxide dismutase, acetylcholine, and other compounds on the release of nitric oxide (NO) by measuring the relaxation responses of aortic rings, with and without intact endothelium, taken from rabbits under various experimental conditions. The aorta of female rabbits released a greater amount of NO than did that of oophorectomized females and male rabbits. The greater basal release of NO in female rabbits was decreased in animals with atherosclerosis induced by a high cholesterol diet. We also investigated the effect of estrogen on endothelial, neuronal and inducible NO synthase (NOS), NOS-3, NOS-1 and NOS-2, respectively. Preincubation with a physiologic concentration of 17 beta-estradiol (10(-12) to 10(-8) M) over 8 h significantly enhanced the activity of NOS-3 in the endothelial cells of cultured human umbilical vein and bovine aortas. 17 beta-Estradiol also enhanced the release of NO from endothelial cells as measured by an NO selective meter and NO2-/N/3-, metabolites of NO. Western blot showed a similar effect of 17 beta-estradiol on NO. Estrogen increased NOS-3 via a receptor-mediated system. Low concentrations of 17 beta-estradiol (10(-10) to 10(-8) M) enhanced the activity of crude NOS-1 in the cytosolic fraction of rabbit cerebella. Partially purified NOS-1, obtained from the cytosolic fraction by DEAE column chromatography, had a similar response to estrogen. Estrogen at a low dose enhanced the fluorescence of dansyl calmodulin and augmented it in high doses. We also investigated the effect of estrogen on NOS-2. When J774 cells, a murine macrophage cell line, were incubated with interferon-r and lipopolysaccharide, NOS-2 was induced and a large amount of NO was released. Pre- or co-incubation of 17 beta-estradiol inhibited the induction of NOS-2 protein and NO release. The estrogen receptor antagonists, tamoxifen and ICI 182780, inhibited that effect of 17 beta-estradiol. 17 beta-Estradiol inhibited the induction of NOS-2 by a receptor-mediated system. These results may offer a new mechanism for the anti-atherosclerotic effect of 17 beta-estradiol.
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PMID:Effect of estrogen on isoforms of nitric oxide synthase: possible mechanism of anti-atherosclerotic effect of estrogen. 918 36


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