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

Diabetic patients with hypertriglyceridemia frequently develop atherosclerosis. Because superoxide (O2-) is suspected to play an important role in the initiation of atherosclerosis, we investigated whether an abnormal amount of O2- was produced by circulating mononuclear cells of patients with both diabetes mellitus and hypertriglyceridemia. The rate of production of superoxide dismutase-inhibitable O2- was measured when cells were stimulated by either 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) or by opsonized zymosan (OZ). In addition, the rates of O2- production by mononuclear cells drawn from three other groups (normal, solely diabetic, and solely hypertriglyceridemic) were determined. We found that the rate of O2- production by mononuclear cells from the diabetic hypertriglyceridemic group was significantly higher than that from normal, diabetic, and hypertriglyceridemic groups. When the rates of O2- production by mononuclear cells were plotted against the levels of plasma triglyceride for all individuals tested, they correlated positively (r = .73 in PMA stimulation and r = .79 in OZ stimulation, P less than .01). However, the rate of O2- production did not relate to other parameters, i.e., plasma cholesterol level, hemoglobin A1 level in erythrocytes, and the molar ratio of free cholesterol to phospholipid in mononuclear cells. Thus, we concluded that the observed elevated rate of O2- production in the diabetic hypertriglyceridemic mononuclear cells was a reflection of a hypertriglyceridemic condition and was not unique to the diabetic hypertriglyceridemic condition. Also, O2- may be involved in the pathogenesis of atherosclerosis in diabetic hypertriglyceridemic patients when atherogenic factors specific to diabetes are concomitantly present.
 ...
PMID:Increased superoxide production by mononuclear cells of patients with hypertriglyceridemia and diabetes. 283 56

We have studied the ability of particulate stimuli to induce the release of reactive oxygen metabolites from sub-cultured monolayers of human endothelial cells. Basal release of superoxide (O2-) and hydrogen peroxide from undisturbed monolayers was very low (108 pmol O2- and 75 pmol H2O2 in 3 h from dishes of 3 X 10(5) cells). Addition of 1-micron diameter polystyrene microspheres, which were phagocytosed by the cells progressively, caused a dramatic increase in release of both metabolites; by 3 h, a 13.5- and 6.6-fold increase over controls was observed respectively (P less than 0.001). Addition of formaldehyde-fixed human platelets or chylomicron-size lipid particles also increased production of reactive oxygen species. Similar rises in H2O2 and O2- production were induced by treatment with 10(-7) M phorbol myristate acetate. Pretreatment of endothelial cells with neuraminidase, heparinase or heparitinase to alter their glycocalyx composition substantially enhanced the effect of microspheres on H2O2 and O2- generation. We conclude that the interactions of particles, including platelets and lipids, with endothelial cells leads to the generation of significant pericellular levels of reactive oxygen species. These metabolites can oxidise a wide variety of nearby molecules, leading to cell damage and altered uptake characteristics for lipoproteins containing peroxidized lipids. These effects are exacerbated when endothelial cell glycocalyx composition is disrupted.
Atherosclerosis 1988 Jul
PMID:Generation of reactive oxygen metabolites by phagocytosing endothelial cells. 285 Aug 6

The effects of prostaglandin (PG) E1, PGE2, the stable prostacyclin analogue Iloprost, and PGF2 alpha on low density lipoprotein (LDL) receptor activity and cholesterol synthesis were investigated in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 45 hr in a lipid-free medium resulted in an increase in the rate of cholesterol synthesis from [14C]acetate and the high affinity accumulation and degradation of 125I-labeled LDL. Addition of PGE1 in increasing concentrations to the incubation medium inhibited cholesterol synthesis and the specific accumulation and degradation of 125I-labeled LDL; at a concentration of 10 microM, the inhibitions were 61%, 70%, and 67%, respectively, after an incubation of 20 hr. The effects of PGE2 and Iloprost were similar. The action of the prostaglandins on LDL receptor activity appeared to be mediated by a decrease in the number of LDL receptors and not by a change in the binding affinity. The prostaglandins yielded sigmoidal log concentration-effect curves. In contrast, PGF2 alpha had no influence on cholesterol synthesis or LDL receptor activity up to a concentration of 10 microM. PGE1, PGE2, and Iloprost, but not PGF2 alpha, led to an increase in the concentration of intracellular cyclic AMP. Dibutyryl cyclic AMP mimicked the effects of the E-prostaglandins and Iloprost on the LDL receptor activity. The results suggest that PGE1, PGE2, and prostacyclin affect LDL receptor activity and cholesterol synthesis and, therefore, may play a role in the regulation of cholesterol homeostasis and in the development of atherosclerosis.
 ...
PMID:Effects of prostaglandins on LDL receptor activity and cholesterol synthesis in freshly isolated human mononuclear leukocytes. 285 53

The aortic endothelium of inherited cataract rats (ICR), which spontaneously develop cataracts and neutrophilia, was examined by scanning electron microscopy using silver nitrate staining and pressure fixation. In ICR aged 4 weeks, the luminal surface of the aorta was similar to that in Wistar rats from which they had been derived. However, 8 weeks after birth, endothelial cells were upraised and partially detached from an underlying tissue. At 16 weeks, morphological changes exhibited by such detaching cells were more evident than at 8 weeks and fibrin was seen to be adhering to the surface of these cells; no platelet involvement was noted, however. Oral administration of DL-alpha-tocopheryl acetate for 2 weeks resulted in a reduction in the extent of endothelial injury and the luminal surface of the aorta became similar to that seen in 4- or 8-week-old animals. We found that the number of age-associated spontaneous injuries occurring in the aortic endothelium of ICR could be reduced by tocopherol administration.
Atherosclerosis 1989 Jan
PMID:Spontaneous injuries in the aortic endothelium of the inherited cataract rats and their prevention by tocopherol. A study by scanning electron microscopy. 293 Jun 12

Adhesion of leukocytes to the aortic endothelium was studied in specific pathogen-free (SPF) and conventional rats and in SPF rats with diet-induced hypercholesterolemia. Nonspecific esterase activity with alpha-naphthyl acetate as substrate was used to characterize the adhered cells. Phagocytic activity was determined by injecting i.v. 0.1-0.4 ml/100 g doses of Monastral blue B (MbB). Adhesion in SPF rats was 8 +/- 4 esterase (+) cells/mm2. Adhesion in conventional rats was of the same order except in 2 cases with antibodies to Mycoplasma pulmonis and Kilham rat virus, where adhesion was 44 and 68 esterase (+) cells/mm2, respectively. For all MbB doses studied, phagocytic activity arose in a percentage of the adherent cells, ranging from 5 to 85%. Rats fed the hyperlipidic diet for 15 days developed severe hypercholesterolemia and adhesion was drastically increased to 200-700 esterase (+) cells/mm2. Results indicate that: (1) spontaneous pathology in rats may produce an increased adhesion of leukocytes to the endothelium, and (2) phagocytic activity is only expressed in a fraction of the esterase (+) cells adhered to the endothelium.
Atherosclerosis 1989 Jan
PMID:Adhesion of leukocytes to the aortic endothelium of conventional, specific pathogen free (SPF) and hypercholesterolemic SPF rats. 293 Jun 16

Human aortic smooth muscle cells were cultured in the presence of sera from 7 normolipidemic women before and after treatment with high-dose medroxyprogesterone acetate, which caused 16% and 25% decreases in serum cholesterol and HDL-cholesterol concentrations, respectively. As assessed by cell counting and by DNA determination the growth of the cells was retarded significantly in the presence of sera taken after the treatment. At the same time, there were no marked changes in the incorporation rate of [3H]proline into collagen or [3H]glucosamine into hyaluronic acid by the cells. The results indicate that: (1) the mitogenicity of human serum can be altered by drug treatment of serum donors, (2) simultaneously with a lowering of serum lipids in man in vivo, a decreased mitogenicity of sera occurs in vitro.
Atherosclerosis 1987 Oct
PMID:Growth of human aortic smooth muscle cells cultured with human serum is retarded when serum lipids are lowered by medroxyprogesterone. 296 Mar 27

Fibroblasts from patients with homozygous familial hypercholesterolemia (FH), a disease characterized by accelerated atherogenesis, are known to lack functional low-density-lipoprotein receptors, which ultimately results in increased cholesterol biosynthesis in the cultured cells. [14C]Acetate incorporation in these cells was compared to that of normal fibroblasts and to fibroblasts from patients with Down's syndrome, a disease in which atherosclerosis is rare. Total [14C]acetate incorporation did not differ significantly between normal and Down's fibroblasts, nor did its partitioning into the hexane-extractable and aqueous fractions of the cell hydrolysates. [14C]Acetate incorporation was much greater in FH cells in both the aqueous and hexane-extractable fractions. Preincubation in fetal bovine serum increased acetate incorporation only by FH cells, while 50 micrograms low-density lipoprotein/ml medium depressed acetate incorporation in all three groups. A C27 sterol, identified by gas chromatography-mass spectrometry as a probable isomer of cholesterol, was present in small amounts in FH fibroblasts, but was not detectable in the normal or Down's cells. The absolute amounts of [14C]acetate incorporated into the non-sterol lipids were greater in the FH fibroblasts, indicating that these cells may have to synthesize, in addition to cholesterol, other required cellular lipids which are delivered to the normal cells by low-density lipoproteins.
 ...
PMID:[14C]acetate incorporation by cultured normal, familial hypercholesterolemia and Down's syndrome fibroblasts. 296 64

The effect of epinephrine on 125I-low density lipoprotein (LDL) uptake and cholesterol metabolism was investigated after a 24 hours pretreatment of cultured human fibroblasts. Epinephrine decreased LDL uptake (binding + internalization) and degradation in a dose-dependent manner. Cholesterol synthesis from 14C sodium acetate and cholesterol esterification measured by 14C oleic acid incorporation into cholesteryl esters were also decreased. These results are in agreement with the general view that epinephrine increases cyclic AMP intracellular level, as it was previously demonstrated that dibutyryl cyclic AMP or isoproterenol treatment of cultured fibroblasts had similar effect on these pathways. The decrease in LDL processing induced by epinephrine could be involved in the worsening effect of epinephrine on atherosclerosis.
 ...
PMID:Epinephrine decreases low density lipoprotein processing and lipid synthesis in cultured human fibroblasts. 300 79

Production of prostacyclin by endothelial cells is considered to be important in rendering the vessel wall nonthrombogenic. Cigarette smoking is an important risk factor in the pathogenesis of atherosclerosis. Here we show that the incubation of cultured human endothelial cells with a cigarette smoke condensate impaired the basal prostacyclin release. Also, the enhanced release of prostacyclin provoked by phorbol myristate acetate was inhibited by cigarette smoke condensate. Furthermore, cigarette smoke condensate impaired the thrombin-induced prostacyclin production. The production of prostacyclin from exogenous arachidonate was not affected by cigarette smoke condensate, indicating that cigarette smoke condensate constituents exert their inhibitory properties on the level of arachidonate mobilization from cellular phospholipids, rather than on cyclooxygenase or prostaglandin synthetase. The effects noted for cigarette smoke condensate could not be attributed to the cigarette smoke constituents nicotine and cadmium. While inhibiting the endothelial cell prostacyclin production significantly, cigarette smoke condensate did not cause cell death or impairment of secretory function, as measured by the release of von Willebrand factor. This in vitro study shows that impairment of an endothelial cell function is related to a risk factor for atherosclerosis.
 ...
PMID:Cigarette smoke impairs endothelial cell prostacyclin production. 308

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.
 ...
PMID:Effect of administration and withdrawal of oral contraceptive pills on serum lipids and lipoproteins. 316 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>