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

A nonhuman primate model was developed to study the effects of oral contraceptives on lipoproteins and atherosclerosis. Cynomolgus macaques were selected because of their susceptibility to diet-induced atherosclerosis and because their reproductive physiology, menstrual cycle, and circulating sex hormone patterns are similar to those of human females. The first study compared a vaginal ring containing levonorgestrel and estradiol with an oral contraceptive containing norgestrel and ethinyl estradiol. A second study compared two oral combinations: norgestrel-ethinyl estradiol and ethynodiol diacetate-ethinyl estradiol. As predicted, use of all the contraceptives led to lowering of high-density lipoprotein cholesterol levels. However, contrary to what might be expected, use of the ethinyl estradiol-containing oral contraceptives did not lead to an increase in the prevalence or extent of atherosclerosis. We concluded that ethinyl estradiol neutralized the atherogenic influence of the progestin component of oral contraceptives.
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PMID:Oral contraceptives, lipoproteins, and atherosclerosis. 222 Sep 63

Studies of both human and nonhuman primates show an inverse relationship between high-density lipoprotein (HDL) cholesterol concentrations and coronary artery atherosclerosis. For this reason, there has been concern that the HDL cholesterol-lowering effect of oral contraceptives might exacerbate coronary artery atherosclerosis. We studied three groups of adult female cynomolgus macaques fed a moderately atherogenic diet: a control group, a group given ethinyl estradiol and norgestrel, and another group given ethinyl estradiol and ethynodiol diacetate. Norgestrel and ethynodiol diacetate, co-administered with ethinyl estradiol, lowered the plasma concentrations of HDL cholesterol. However, the extent of coronary artery atherosclerosis was lessened by both contraceptives, especially among females at high risk based on their plasma lipid profiles.
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PMID:Oral contraceptives and coronary artery atherosclerosis of cynomolgus monkeys. 230 Mar 48

The structure of lipoproteins is described, followed by a description of the structure and function of low density lipoproteins (LDL) which carry cholesterol to cells, and high density lipoproteins (HDL) which remove cholesterol. The process of atherosclerosis is then indicated. When LDL accumulates in plasma, it is deposited in macrophages which metabolize all the components of LDL except the cholesterol ester which becomes a foam cell. HDL converts foam cells back to macrophages. The presence of HDL and HDL2 allows foam cells to secrete cytoplasmic cholesterol and an apoprotein E which coats HDL2 and allows the recognition and removal of cholesterol in blood and by receptors in he liver. Atherosclerosis can be predicted from the effect of the HDL and LDL on foam cell formation, i.e., more foam cells means more HDL, particularly HDL2, and the less likely atherosclerosis will develop. The link between oral contraceptives (OCs) and atherosclerosis is that with estrogen LDL cholesterol levels decrease, while there are increases with progestins; HDL and HDL2 increase with estrogen and decrease with progestins. HDL3 is unaffected by estrogen. The effects of progestins are dependent on a number of other factors. Longterm clinical trials of OCs and their effects on lipoproteins are identified from Johns Hopkins and George Washington University studies. The longterm trail results are given. Total cholesterol rose regardless of the 3 different progestins. Compounds containing dl-norgestrel in higher doses raised LDL levels more than ethynodiol diacetate or norethindrone. In low doses, levels of LDL also rose but ethynodiol diacetate rose least in 6 months. Apoprotein B also rose in a similar fashion. Norgestrel lowers HDL considerably and HDL2 in higher or lower doses; there were more differences in ethynodiol diacetate or norethindrone. All 3 preparations raised HDL3 similarly. Norgestrel decreases apoprotein levels in high doses and apoprotein is unaffected at low doses; low apoprotein is linked to coronary artery disease. Increases occurred with ethynodiol diacetate and norethindrone. New triphasic compounds are under investigation, and show low HDL at 6 but not 12 months, but consistently raise LDL. Lipoprotein phospholipids research findings are also revealed as well as other related research. Adverse effects may be seen for many years after OC use, so low doses are recommended.
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PMID:Effects of oral contraceptives on circulating lipids and lipoproteins: maximizing benefit, minimizing risk. 257 64

Studies on the use of oral contraceptives in the West have shown that they induce changes in total serum cholesterol, triglycerides, high density lipoproteins, low density lipoproteins, and very low density lipoproteins -- changes which are implicated in the development of atherosclerosis. In India, however, women consume low fats, low cholesterol and fewer calories; they drink less alcohol and rarely smoke; and they engage in more physical activities. 2 groups of Indian women were tested for lipid metabolism alterations during and after use of oral contraceptives supplied by the Indian government. 1 group of 23 women, aged 20-30, received low dose oral contraceptives containing 30 ug ethinyl estradiol and 1 mg of norethisterone acetate, and their serum lipid levels were tested after 3 and 6 months of use. A 2nd group of 12 multiparas, aged 25-35, who had been taking oral contraceptives for 1 1/2 to 2 years (either 50 um ethinyl estradiol and .5 mg norgestrel, called Ovular or Primovlar-50, or 30 ug ethinyl estradiol and .5 mg ethynodiol diacetate, called Ovular-50) were examined for serum lipid levels 3 and 6 months after withdrawal from the pills. In the 1st group no significant change was observed in any lipid fraction after 3 or 6 months of oral contraceptive use. In the 2nd group low density lipoprotein levels were significantly lower 3 and 6 months after withdrawal, in comparison with the basal values of the 1st group. It is concluded that low dose oral contraceptives supplied by the Indian government have no significant effect on serum lipids after 6 months of use.
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PMID:Effect of administration and withdrawal of oral contraceptive pills on serum lipids and lipoproteins. 316 63

In previous studies, it was shown that a lysine deficient diet reduces the severity of aortic cholesterol atherosclerosis in rabbits. Feeding 1-amino-3-imino N,N' propene diacetate (AIPD) produced 2 metabolic by products with active aldehyde groups 1-amino propenal acetic acid (APA) and malonyldialdehyde (MDA) that transiently block the lysine epsilon-amino groups of all proteins and lipoproteins in vivo. This paper reports the effects of blocking the lysine free epsilon-amino groups of all lipoproteins on 2 different types of cholesterol atherosclerosis; (1) A proliferative-type cholesterol atherosclerosis containing a high proportion of spindle-shaped myogenic foam cells rich in collagen and alcian blue-stainable material produced by feeding a diet containing cholesterol, peanut oil, ethanol and butylated hydroxyanisole and (2) cholesterol atherosclerosis containing a high proportion of polyhedral-shaped nonmyogenic macrophage-type foam cells produced by feeding cholesterol and oleic acid. After 14 weeks on the diets the mean +/- SD percent of intimal aortic area covered with the myogenic-type atherosclerosis in the control peanut oil-fed group was 34 +/- 6% and this was reduced to 13 +/- 3% in the peanut oil AIPD group. In contrast, after 14 weeks in the control oleic acid group the severity of atherosclerosis was 14 +/- 4% and this was increased to 36 +/- 7% in the oleic acid AIPD group. Aortic cholesterol concentration was decreased in the AIPD peanut oil group relative to its control but was increased in the AIPD oleic acid group relative to its control group. A higher concentration of AIPD metabolites accumulated in the atherosclerotic lesions of the oleic AIPD group than in the peanut oil AIPD group indicating that a larger amount of lysine blocked lipoprotein accumulated in the macrophage-rich lesions of the oleic acid AIPD group than in the myogenic-rich lesions of the peanut oil AIPD group. Blocking lysine epsilon-amino groups in vivo by feeding AIPD did not modify DNA synthesis in the aortae of either AIPD group relative to their control groups.
Atherosclerosis 1985 Oct
PMID:Modification of two types of cholesterol atherosclerosis in rabbits by blocking lipoprotein lysine epsilon-amino groups. 393 26

The ultrastructural effects of a single brief intra-arterial infusion of palmitic, linoleic and acetoacetic acid on the arterial endothelium of the rat were investigated, and the following results obtained: (1) Palmitic acid, infused at a concentration of 4 mM/l, damaged the arterial lining by producing large cytoplasmic clefts and occasional blebbing and lysis of the endothelial cells. By contrast, linoleic acid, infused at the same concentration, had no damaging effects on arterial endothelium. (2) Acetoacetic acid damaged the arterial wall when infused at concentrations of 0.2 mM/l or higher by inducing extreme swelling and loss of cristae of the mitochondria in arterial endothelium and myocytes. The above results raise the possibility that (a) high saturated fatty acid diets may promote atherosclerosis not only by inducing hypercholesterolemia but also by injuring the arterial lining, and (b) diabetes may promote atherosclerosis not only by inducing hyperlipemia but also by damaging the arterial wall during periods of uncontrolled ketoacidosis.
Atherosclerosis
PMID:Arterial effects of palmitic, linoleic and acetoacetic acid. 722 70

The possibility that risk of a atherosclerosis complication increases with oral contraceptive use was examined by studying the effect of oral pill containing 0.067 mg menstranol and 0.667 mg ehtynodiol diacetate/kg body weight on the metabolism of lipids in female rats fed a hypercholesterolemic diet for three months. Experimental group clearly exhibited higher levels of triglycerides and cholesterol in plasma and tissues, increase in aorta observed to be two folds. Increased hepatic cholesterogenesis was noted with treatment of oral contraceptive as indicated by higher activity of HMG-CoA reductase. Activity of lipoprotein lipase of extrahepatic tissue was depressed in experimental group. Activity of plasma LCAT, an enzyme involved in the transport of cholesterol from tissues, was also lower with treatment of oral contraceptive. However, activity of malic enzyme and glucose-6-phosphate dehydrogenase enhanced considerably with administration of oral pill. The increase in plasma and aortic cholesterol levels, increase in LDL+VLDL cholesterol and considerable decrease in HDL cholesterol in animals treated with oral contraceptives and fed with atherogenic diet, indicates that prolonged administration of oral pill may predispose towards atherosclerosis.
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PMID:Role of oral contraceptive in atherosclerosis. 792 21

Nitric oxide (NO) has been shown to inhibit platelet adhesion and aggregation, but there are no reports on its interaction with the coagulation system. We investigated the effect of the L-arginine analogues, N-nitro-L-arginine (LNA), N(G)-nitro-L-arginine methyl ester (L-NAME), and N(G)-monomethyl-L arginine (L-NMMA), competitive inhibitors of NO production, on endothelial-surface heparan sulfate. Addition of LNA to porcine aortic endothelial cells reduced 125I-labeled antithrombin III binding to the cell surface heparan sulfate in a dose- and time-dependent fashion. Significant inhibition was observed with 1 mM LNA, and the maximal suppression (-50% of control) occurred at 10 mM LNA after 12 h. L-NAME (1 mM) and L-NMMA (1 mM) also significantly inhibited the antithrombin III binding. The iron chelator desferrioxamine significantly prevented the reduction of antithrombin III binding to LNA-treated cells. We further investigated the effect of L-NAME on intracellular oxidative stress of endothelial cells using a hydroperoxide-sensitive fluorochrome, carboxy-dichloro-dihydrofluorescein diacetate bisacetoxymethyl ester probe, and revealed that inhibition of NO synthesis by L-NAME led to a marked increase in intracellular oxidative stress. These results demonstrated that the prolonged inhibition of NO synthesis in porcine aortic endothelial cells decreases the expression of anticoagulant heparan sulfate on endothelial cells through the increase in intracellular oxidative stress, perhaps comprising another mechanism by which NO affects the coagulation system in the vasculature.
Atherosclerosis 1997 Nov
PMID:Endothelial-derived nitric oxide preserves anticoagulant heparan sulfate expression in cultured porcine aortic endothelial cells. 939 68

To clarify the mechanism of cellular injury through the nonenzymatic reaction of glucose with proteins, we studied the cytotoxic effect of glycated bovine serum albumin on cultured smooth muscle cells in the presence of cupric ion. Glycated proteins were prepared by incubating bovine serum albumin with 0.5 M D-glucose in 0.3 M sodium phosphate buffer at 37 degrees C for 2, 4 and 16 weeks (g-BSA-2, g-BSA-4 and g-BSA-16, respectively). Early glycation products, such as fructosamine, were formed more than two weeks after incubation. However, the immunoreactivity of glycated proteins to anti-AGE antibody was 12-fold higher in g-BSA-16 than in g-BSA-2. Both g-BSA-2 and g-BSA-16 showed a concentration-dependent cytotoxicity in smooth muscle cells in the presence of 80 microM cupric ion by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) dye reduction assay and dye exclusion test. Flow cytometry and spectrofluorophotometry using dihydrorhodamine 123 showed that the extracellular generation of oxidants was dose-dependently enhanced with increasing concentrations of g-BSA-2 or g-BSA-16 in the presence of cupric ion. However, no difference was observed in the intracellular generation of oxidants between the presence and absence of glycated proteins by flow cytometry using 2', 7'-dichlorofluorescein diacetate. Cytotoxicity and oxidant generation were prevented by catalase and tiron, but not by superoxide dismutase or mannitol, a hydroxyl radical scavenger. These results indicate that smooth muscle cells may be damaged by reactive oxygen species which are produced extracellularly by the interaction with the early glycation products and cupric ion, and suggest that hydrogen peroxide may be a candidate for reactive oxygen species which contribute to such oxidative damage of smooth muscle cells.
Atherosclerosis 1998 Feb
PMID:Oxidative damage of vascular smooth muscle cells by the glycated protein-cupric ion system. 954 97

Our previous experiments demonstrated upregulation of the renin-angiotensin system in macrophages, including angiotensin II type 1 (AT1) and type 2 (AT2) receptors, during transformation from monocytes. We investigated the role of angiotensin II in oxidative stress of monocytes/macrophages, which plays a role in the advance of atherosclerosis. THP1, a human monocytic leukemia cell line, was differentiated to macrophages by adding of phorbol 12-myristate 13-acetate for 24 hours. The intracellular production of peroxide was measured by a cytofluorometric assay with 2', 7'-dichlorofluorescein-diacetate with a flow cytometer scan. Peroxide was detected in monocytes and upregulated during the transformation to macrophages by 3.18+/-0.52 times in relative fluorescein of peak value (P<0.01). Angiotensin II (1 micromol/L) induced oxidative stress in macrophages, with the peak at 15 minutes by 451+/-223%, and returned to the control level within 1 hour. EC50 was 5.4x10(-9) mol/L. AT1 antagonist (CV11974, 1 micromol/L) significantly decreased angiotensin II-induced oxidative stress in macrophages, but AT2 antagonist (PD123319, 1 micromol/L) did not. Of interest, AT1 antagonist also decreased basal levels of peroxide production in macrophages in a dose-dependent manner. These results suggest that upregulation of the expression of AT1 receptor in macrophages contributes in part to upregulation of peroxide production. AT1 receptor antagonists may be useful to suppress oxidative stress of macrophages in atherosclerotic lesions.
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PMID:Angiotensin II type 1 receptor-mediated peroxide production in human macrophages. 993 Nov 26


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