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

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
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PMID:Endothelial function and hemostasis. 1079 71

Glycated lipoproteins, which elevate the blood in diabetic patients, cause direct attenuation of endothelial function. Increased glycation of apolipoproteins may play a trigger role in the accelerated development of atherosclerosis in the patient with diabetes. Here we assessed whether glycated lipoproteins affect on the endothelial function with particular emphasis on the role of reactive oxygen species in vitro. Incubation of human aortic endothelial cells(HAEC) with glycated LDL had little influence on the expression of antioxidant enzymes such as nitric oxide synthase(NOS), Cu2+Zn(2+)-superoxide dismutase (Cu2+Zn(2+)-SOD), catalase, and p22 phox in the cells. In contrast, exposure of glycated HDL induced a marked decrease of Cu2+Zn(2+)-SOD, catalase, and endothelial NOS as well as a slight increase of p22 phox in HAEC in term of both protein and mRNA expression, suggesting that increased formation of reactive oxygen species such as O2- and OH radical participate in the deterioration for the function of vascular endothelial cells in diabetic patients.
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PMID:[Expression of reactive oxygen-species related enzymes in endothelial cells stimulated with glycated lipoproteins]. 1081 Aug 80

Oxygen free radicals as well as immunological reactions have been suggested to play important roles in atherogenesis and other pathological processes of the blood vessel wall. We have previously shown that the vascular wall contains exceptionally large amounts of extracellular superoxide dismutase (EC-SOD) and that the enzyme is produced and secreted to the extracellular space by the smooth muscle cells. In this work, we studied the influence of inflammatory cytokines on vascular smooth muscle cell expression of EC-SOD, the mitochondrial manganese superoxide dismutase (Mn-SOD) and the cytosolic copper zinc superoxide dismutase (CuZn-SOD). The expression of EC-SOD was up-regulated by interferon-gamma (IFN-gamma) and interleukin 4 (IL-4). and was down-regulated by tumor necrosis factor-alpha (TNF-alpha). The ratio between the maximal stimulation and depression observed was around 20-fold. The responses were slow and developed over periods of several days. The Mn-SOD activity was strongly up-regulated by TNF-alpha and IL-1alpha and moderately by IFN-gamma. The CuZn-SOD activity of the smooth muscle cells was not significantly influenced by any of the cytokines. The findings suggest that large changes in the SOD isoenzymes might occur in vascular diseases, significantly altering the susceptibility of the vascular wall to adverse effects of the superoxide radical.
Atherosclerosis 2000 Aug
PMID:Multiple cytokines regulate the expression of extracellular superoxide dismutase in human vascular smooth muscle cells. 1092 20

Manganese superoxide dismutase (MnSOD), an inductive antioxidant enzyme, can protect cells from oxidative injury to the mitochondria. The elevation of MnSOD activity in cells can effectively prevent many diseases associated with oxidative stress. Polysaccharide Krestin (PSK), a kind of protein-bound polysaccharide extracted from Coriolus versicolor, is used as an immune response modifier in anti-tumor therapy. We have previously found that PSK could alleviate the oxidative injury that oxidized low density lipoprotein (Ox-LDL) brought to monocytes/macrophages, and therefore had some preventive or therapeutic effect on atherosclerosis. In order to find out if the effects of PSK were associated with the alteration ofantioxidant enzymes, we investigated its effect on MnSOD activity and gene expression in mouse peritoneal macrophages. The results showed that PSK could enhance SOD activity and increase the contents ofMnSOD mRNA in mouse peritoneal macrophages. Furthermore, the induction of MnSOD by PSK could be blocked by cycloheximide and actinomycin D.
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PMID:Polysaccharide Krestin enhances manganese superoxide dismutase activity and mRNA expression in mouse peritoneal macrophages. 1115 46

ADVERSE EFFECTS OF OXYGEN: Adverse effect of oxygen on anaerobes implies oxidation of the basic cell constituents NAD(P)H, thiols, iron-sulphur proteins, pteridines and others) and inactivation of the essential components of the active site of enzymes. Oxygen can also adversely affect the aerobes, especially if long-term influence is taken into consideration, while exposition to high-pressure oxygen causes considerable damages. Direct influence of oxygen on aerobes due to slow and limited enzyme inactivation (for example glutamate decarboxylase) and small number of affected "targets" is not responsible for total adverse effects of oxygen. Even in 1954 it was supposed that oxygen free radicals are the most responsible for the adverse effects of oxygen. ATMOSPHERIC (TRIPLET) OXYGEN: Electron configuration of triplet oxygen explains its reactivity since it is a biradical. The reactions of oxygen with non-radicals are possible with participation of transition metals (except zinc), while its reactivity is much more expressed in case of reactions with other radical species. ACTIVE OXYGEN: More reactive forms of oxygen, known as singlet oxygen, can be generated by an input of energy to triplet oxygen. Singlet-oxygen is obtained mainly by photoexcitation in the presence of initiators (methylene blue, chlorophyll etc.) and as a product of reactions of ozone with certain biomolecules. REDUCED FORMS OF OXYGEN: If a single electron is added to the triplet oxygen, it must enter one of the antibonding molecular orbitals and produce the superoxide radical--(O2.-). Addition of one more electron produces peroxide ion--O2(2-), which forms hydro peroxide in presence of H+, the most common two-electron reduction product of oxygen in biological systems. The four-reduction product of oxygen in biological systems is water. SUPEROXIDE RADICAL: The in vivo production of superoxide radical is possible in many different ways mentioned in this paper. This radical species is unstable in water solutions because of dismutation reaction leading to non-enzymic generation of hydroperoxide. The most reactive radical species--hydroxyl radical is produced from hydro peroxide by Fenton or Haber-Weiss reactions in the presence of catalytic transition metals (iron or copper). HYDROXYL RADICAL: Hydroxyl radicals are the most reactive radical species. The way of their generation has been shown in detail in this paper with special emphasis given to Fenton and Haber-Weiss reactions, that is, transition metals (iron and copper) as catalizators for these reactions. The reactivity of hydroxyl radical can be recognized by monitoring the second-order rate constants for reactions of the hydroxyl radical with some organic compounds in aqueous solution presented in this paper. Although the number of compounds that can be affected and damaged by hydroxyl radicals is great, until now, attention has been paid mostly to investigation of attacks of these radical species on lipids, proteins and DNA. LIPID PEROXIDATION: Radicals react with lipids and cause oxidative destruction of unsaturated, that is, polyunsaturated fatty acids, known as lipid peroxidation. Both lipids in biological systems and lipids as food constituents are submitted to this process. Lipid peroxidation is a chain reaction and its mechanism has been shown in detail in this paper. Lipid peroxidation in cells leads to direct damage of cell membranes with indirect damages of other cell constituents, caused by reactivity of secondary products of this reaction, aldehydes. This complex reaction is responsible for damages of many tissues and progress of some diseases (atherosclerosis). OXIDATIVE STRESS: Protection of an organism from oxygen free radicals implies activity of enzymatic (catalase, SOD, glutathione peroxidase, glutathione reductase etc.) and nonenzymatic (vitamin E. vitamin C. glutathione, uric acid etc.) systems of protection. Disturbance of the balance between production of oxygen free radicals (or some other radical species) and activity of antioxidative system of protection causes the so called oxidative stress. An organism can tolerate a mild oxidative stress but a higher disturbance between the production of free radicals and the activity of the antioxidative protection results in lipid protein and DNA as well as numerous diseases.
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PMID:[Free oxygen radiacals and kidney diseases--part I]. 1132 Jul 27

The term 'platelet-derived growth factor' (PDGF) refers to a family of disulphide-bonded dimeric isoforms that are important for growth, survival and function in several types of connective tissue cell. So far, three different PDGF chains have been identified - the classical PDGF-A and PDGF-B and the recently identified PDGF-C. PDGF isoforms (PDGF-AA, AB, BB and CC) exert their cellular effects by differential binding to two receptor tyrosine kinases. The PDGF alpha-receptor (PDGFR-alpha) binds to all three PDGF chains, whereas the beta-receptor (PDGFR-beta) binds only to PDGF-B. Gene-targeting studies using mice have shown that the genes for PDGF-A and PDGF-B, as well as the two PDGFR genes, are essential for normal development. Furthermore, overexpression of PDGFs is linked to different pathological conditions, including malignancies, atherosclerosis and fibroproliferative diseases. Here we have identify and characterize a fourth member of the PDGF family, PDGF-D. PDGF-D has a two-domain structure similar to PDGF-C and is secreted as a disulphide-linked homodimer, PDGF-DD. Upon limited proteolysis, PDGF-DD is activated and becomes a specific agonistic ligand for PDGFR-beta. PDGF-DD is the first known PDGFR-beta-specific ligand, and its unique receptor specificity indicates that it may be important for development and pathophysiology in several organs.
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PMID:PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. 1133 81

In the early atherosclerotic lesion, monocytes accumulate at sites of inflammation and endothelial injury. Platelet-derived growth factor (PDGF), produced for example by macrophages, is a chemoattractant for smooth muscle cells and possibly also for macrophages. During early differentiation into macrophages, human monocytes (early hMDM) showed lower expression of PDGF alpha-receptor (PDGF-Ralpha) than beta-receptor (PDGF-Rbeta) mRNA. Early hMDM showed increased random motility (chemokinesis) in the presence of PDGF of the long (BB(L)) but not short (BB(S)) B-chain homodimer. Neither PDGF-AA(S) nor PDGF-AA(L) affected early hMDM motility. Since increased cytokine levels accompany inflammation, the influence of interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) on PDGF-R expression and migratory response were studied. Only PDGF-Ralpha mRNA was highly upregulated by IFN-gamma. TGF-beta only had minor effects on receptor mRNAs. Upregulation of PDGF-Ralpha levels by IFN-gamma was accompanied by significantly increased migration (chemotaxis) towards PDGF-AA(L) only. Consequently, IFN-gamma modulates PDGF-Rs expression in early hMDM and, subsequently, the chemotactic activity of PDGF-AA(L) on IFN-gamma-stimulated early hMDM. This suggests that PDGF-AA(L) may be involved in attracting activated monocytes to sites of inflammation and injury.
Atherosclerosis 2001 Jun
PMID:Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-gamma and TGF-beta. 1139 22

Reactive oxygen species have been proposed to play important roles in atherosclerosis. To investigate the protective role of extracellular superoxide dismutase (EC-SOD), its inhibition of endothelial-cell-mediated LDL oxidation was examined. We constructed the recombinant adenovirus AxCAEC-SOD expressing human EC-SOD by CAG promoter. Infection of endothelial cells with AxCAEC-SOD resulted in EC-SOD protein secretion in a dose-dependent manner and a decrease of endothelial-cell-derived superoxide production. Moreover, it was proven to coexist with heparan sulfate by immunohistochemical staining. Endothelial-cell-mediated LDL oxidation enhanced by ferric-sodium EDTA was inhibited by 47% in TBARS formation by AxCAEC-SOD infection. In agarose gel electrophoresis, AxCAEC-SOD decreased the negative charge of oxidized LDL by 50% and suppressed fragmentation of apolipoprotein B. These results suggested that human EC-SOD localized in the extracellular space and reduced endothelial-cell-mediated LDL oxidation. In subendothelial space, EC-SOD bound on heparan sulfate might suppress LDL oxidation through reduction of superoxide anion.
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PMID:Overexpression of EC-SOD suppresses endothelial-cell-mediated LDL oxidation. 1143 76

To compare the chronic effect of several dialytic techniques (bicarbonate dialysis, BHD; acetate free biofiltration, AFB; hemodiafiltration, HDF; paired filtration dialysis, PFD) on atherosclerosis and antioxidant activity, three different indices were created. The first (atherosclerotic index = AI) is formed using the sum of three plasma substances: MDA, Hcy, and Cys (malondialdehyde, homocysteine, cysteine). The second (antioxidant activity index = AOAI) is the sum of five erythrocyte (E) parameters: E-GSH, GPx, CAT, SOD, GR (E-glutathione, E-glutathione peroxidase, E-catalase, E-superoxide dismutase, E-glutathione reductase). The third (defense index = DI) is derived from the previous two: (AOAI - AI). The indices were so expressed as AI in mmol/L, AOAI in U/g hemoglobin (Hb), and DI in arbitrary units. These indices were calculated in 20 controls and 51 chronic HD patients (26 female, 25 male) before, during, and after the first session of the week. HD patients were divided according to their dialytic technique: BHD, n = 35; AFB, n = 5 patients; HDF, n = 7 patients; or PFD = 4 patients. All patients had been treated with a given technique for at least 12 months, before entering the study. As expected, HD patients had AI values higher than controls, both before and after the session, with a mean value of 541 (before) and 331 (after), whereas controls had a mean value of 205. The AOAI was lower than controls, both before and after the session, the mean value being 1,122 (before) and 1,582 (after), that of controls being 2,424. In all cases, PFD gave the best "acute" results; at the end of a PFD session, near normal values of AI, AOAI, and DI (defensive index = AOAI - AI) were obtained.
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PMID:Do different dialytic techniques have different atherosclerotic and antioxidant activities? 1157 29

The consumption of a cholesterol-enriched diet increases the degree of lipid peroxidation, which is one of the early processes of atherosclerosis. The aim of this trial was to determine the antioxidative effects of the citrus bioflavonoid, naringin, a potent cholesterol-lowering agent, compared to the cholesterol-lowering drug, lovastatin, in rabbits fed a high cholesterol diet. Male rabbits were served a high-cholesterol (0.5%, w/w) diet or high-cholesterol diet supplemented with either naringin (0.5% cholesterol, 0.05% naringin, w/w) or lovastatin (0.5% cholesterol, 0.03% lovastatin, w/w) for 8 weeks to determine the plasma and hepatic lipid peroxide, plasma vitamin A and E levels, and hepatic hydrogen peroxide levels, along with the hepatic antioxidant enzyme activities and gene expressions. Only the lovastatin group showed significantly lower plasma and hepatic lipid peroxide levels compared to the control group. The naringin supplementation significantly increased the activities of both hepatic SOD and catalase by 33% and 20%, respectively, whereas the lovastatin supplementation only increased the catalase activity by 23% compared to control group. There was no difference in the GSH-Px activities between the various groups. Content of H2O2 in hepatic mitochondria was significantly lower in groups supplemented with lovastatin and naringin than in control group. However, there was no difference in cytosolic H2O2 content in liver between groups. The concentration of plasma vitamin E was significantly increased by the naringin supplementation. When comparing the antioxidant enzyme gene expression, the mRNA expression of SOD, catalase and GSH-Px was significantly up-regulated in the naringin-supplemented group. Accordingly, these results would appear to indicate that naringin, a citrus bioflavonoid, plays an important role in regulating antioxidative capacities by increasing the SOD and catalase activities, up-regulating the gene expressions of SOD, catalase, and GSH-Px, and protecting the plasma vitamin E. In contrast, lovastatin exhibited an inhibitory effect on the plasma and hepatic lipid peroxidation and increased the hepatic catalase activity in high-cholesterol fed rabbits.
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PMID:Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits. 1172 89


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