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)

The model was established in male rabbits with experimental atherosclerosis, which was induced by diet cholesterol (0.5 g per day for 8 weeks), by means of intravenous injection of one unit of pituitrin (P.P.). To evaluate the effects of aspirin, heparin and viper venom (VV) on this model, 26 male rabbits were divided randomly into four groups: group A (GA) as control, group B (GB) treated with heparin (10mg, i.v.), group C (GC) with VV (0.08 arginine esterase activity units), group D (GD) with both heparin and VV. Aspirin (30 mg) was given orally before experiment. The results showed that the rate of coronary thrombosis was 11.26% in GA, 8.10% in GB, 9.17% in GC, and 7.56% in GD respectively. The difference between each of three treated groups and the control one was significant (P < 0.005, 0.05, 0.001, respectively). Such a difference can also be found between GA and that without oral aspirin (11.26% vs 16.39%, P < 0.001). The beneficial effects of heparin and VV may be due to their inhibitory effects on different steps of thrombosis, i.e., heparin can prolong the coagulation time, and VV can inhibit platelet aggregation and decrease the concentration of plasma fibrinogen. It is concluded that heparin, viper venom, and especially their combination would be useful in the treatment of human acute coronary syndromes.
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PMID:A new animal model of coronary thrombosis and effects of antithrombotic agents. 755 40

As part of the multicenter project entitled "Pathobiological Determinants of Atherosclerosis in Youth (PDAY)," we are testing polymorphisms in candidate genes of atherosclerosis and hypertension for associations with arterial lesions in autopsied young persons. In this study, we used temperature gradient gel electrophoresis (TGGE) to type the Met235-->Thr polymorphism in exon 2 of the angiotensinogen gene (AGT) that is associated with essential hypertension in some human populations. In addition to Met235-->Thr, we detected and sequenced four other TGGE variants in exon 2 of AGT. These included two new amino acid substitutions (Thr209-->Ile and Leu211-->Arg) that were found only among black PDAY cases. The frequency of the Ile209 mutation was 0.002 and the frequency of the Arg211 was 0.006 in 260 black PDAY cases. The other two TGGE variants were Tyr248-->Cys and a T-->C substitution at nucleotide position 171 that had been identified in previous studies. We also developed restriction isotyping for rapid typing of each AGT variant using PCR amplification and digestion with diagnostic restriction enzymes.
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PMID:Detection and characterization of new mutations in the human angiotensinogen gene (AGT). 760 42

Hyperlipidemia contributes to the development of intimal hyperplasia and subsequent accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary supplementation with L-arginine on the development of intimal hyperplasia and the vasomotor function of vein grafts in hypercholesterolemic animals. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were sacrificed at 28 days postoperatively. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery and this diet was continued until harvest. Of these, 10 also received L-arginine (2.25%, 2 g/kg, p.o.) 7 days preoperatively and thereafter until harvest. The last 10 animals were controls. Vein grafts were harvested either for morphology or for in vitro isometric tension studies. Cumulative dose-response curves to norepinephrine, serotonin, and bradykinin were recorded, and following norepinephrine precontraction, relaxation to acetylcholine and sodium nitroprusside were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The addition of L-arginine doubled the serum arginine concentrations. Intimal hyperplasia of both groups of hypercholesterolemic vein grafts contained foam cells and lipid-laden endothelial and smooth muscle cells. There was a 24% reduction in the intimal thickness of vein graft intimal hyperplasia in the L-arginine group compared to that in the hypercholesterolemia group (P < 0.05). All hypercholesterolemic vein grafts were two-fold thicker than in the control group. L-arginine supplementation resulted in the preservation of acetylcholine-mediated relaxation but did not change hypercholesterolemia-induced contractile agonist supersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Control of accelerated vein graft atheroma with the nitric oxide precursor: L-arginine. 763 Jan 34

Cigarette smoking is associated with an increased risk of premature atherosclerosis. The underlying mechanisms responsible for this association are unknown. Recent work from this laboratory has shown that ex vivo exposure to plasma to gas-phase cigarette smoke (CS) produces a rapid inhibition of lecithin-cholesterol acyltransferase (LCAT) activity and crosslinking of HDL-apolipoproteins. The goal of the present study was to investigate the mechanism(s) by which CS inhibited LCAT and modified HDL. When dialyzed human plasma (12 ml) was exposed to the gas-phase of an equivalent of 1/8 of a cigarette (one 'puff') at 15 min intervals for 3 h, LCAT activity was reduced by 76 +/- 1% compared to controls; supplementation of plasma with glutathione produced a dose-dependent protection of LCAT activity where at the highest concentration (1 mM) 78% protection was observed. A similar protection was obtained with N-acetyl cysteine (1 mM). In addition to LCAT inhibition, HDL-apolipoproteins were crosslinked after 3 h exposure of plasma to CS; crosslinking was reduced by the addition of either glutathione or N-acetyl cysteine to plasma. The amino compounds N-acetyl lysine, N-acetyl arginine, and aminoguanidine failed to protect LCAT and HDL indicating a specificity with regard to the ability of free thiols to buffer the deleterious components of CS which inhibited LCAT and crosslinked HDL-apolipoproteins. Since LCAT contains two free cysteine residues (Cys-31 and -184) near the active site of the enzyme, we tested whether pretreatment of plasma with the reversible sulfhydryl modifying compound, 5,5'-dithiobis-2-nitrobenzoic acid (DTNB), could protect LCAT from CS-induced inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gas-phase cigarette smoke inhibits plasma lecithin-cholesterol acyltransferase activity by modification of the enzyme's free thiols. 765 78

Hypercholesterolemia, before atherosclerosis, is known to reduce agonist- (e.g., acetylcholine) mediated nitric oxide (NO) production within 2 weeks of a cholesterol-enriched diet. However, no data exist on the effect of hypercholesterolemia on the basal release of NO from blood vessels. We studied the basal release of NO in rabbit coronary arteries by addition of the NO synthase blocker NG-nitro-L-arginine-methyl ester (L-NAME). Basal release of NO was markedly attenuated 2 weeks after introduction of a 0.5% cholesterol addition to the diet. One week later, the adherence of neutrophils to the coronary endothelium was significantly enhanced (i.e., threefold; p < 0.01 different from control). The increased adhesiveness could be attributed to enhanced endothelial adhesion rather than to changes in the properties of the leukocytes. Both phenomena could be reversed by addition of L-arginine to isolated coronary arteries. Administration of 10 mg/day lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, markedly attenuated both the reduced basal NO production and the increased adhesiveness of the endothelium. These results support the concept that NO is an important protective agent produced by the endothelium to preserve the integrity of the endothelium and may protect it against atherogenesis.
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PMID:Decreased basal nitric oxide release in hypercholesterolemia increases neutrophil adherence to rabbit coronary artery endothelium. 768 5

Nitric oxide is synthesised from an amino acid, L-arginine, by a family of enzymes called nitric oxide (NO) synthase, by most cells in the vessel wall. In healthy vessels, the production of NO is due to the constitutive and calcium dependent NO synthase present in the endothelial cells. On the other hand, when the vascular system is diseased and defense mechanisms are activated, the mediators of inflammatory and immunitary reactions induce an NO synthase non-responsive to calcium which produces large quantities of NO in most of the cells of the vessel wall. Nitric oxide is a liposoluble radical with a short half-life. It plays a central role in the regulation of the motricity and proliferation of blood vessels and in the interaction of the blood cells with the vessel wall. An inadequate production of nitric oxide could play a role in many vascular diseases such as hypertension, atherosclerosis, restenosis or vascular hyporeactivity associated with septicaemic shock.
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PMID:[Nitric oxide and homeostasis of the smooth vascular muscle]. 769 33

Arginine, glutamine, the long chain polyunsaturated omega-3 and omega-6 fatty acids, and, to a lesser extent, ribonucleic acid and the vitamins E, C, and A have pharmacologic effects when given in amounts in excess of what is needed to prevent nutritional deficiency. These effects are exerted primarily via the immune system, and immunoenhancing diets that embody the recently developed principles of nutritional pharmacology have been shown to reduce infectious complications by approximately 75% in surgical patients and hospital stay by more than 20% in surgical patients and patients in the intensive care unit in three independent, prospective, randomized studies, two of which were double-blinded. These findings suggest that specialized diets can be designed that will be of benefit to patients with cancer, atherosclerosis, intestinal diseases, autoimmune diseases, infections, and trauma. However, the interaction of these nutrients in pharmacologic amounts with standard pharmacologic drugs is largely unknown, as are the effects of long-term administration of specialized diets to treat these conditions.
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PMID:Immunoenhancement via enteral nutrition. 769 65

The bioavailability of nitric oxide (NO) in the human coronary circulation at rest and after acetylcholine (ACH)-induced vasodilation was investigated in 32 patients with angiographically normal coronary arteries. The effects of intracoronary L-NG monomethyl arginine (L-NMMA) were investigated at rest and after ACH, sodium nitroprusside, and adenosine. L-NMMA (64 mumol/min) increased resting coronary vascular resistance by 22% (P < 0.001), reduced distal epicardial coronary artery diameter by 12.6% (P < 0.001), and inhibited ACH-induced coronary epicardial and microvascular vasodilation. These effects were reversed with intracoronary L-arginine. L-NMMA did not inhibit dilation in response to sodium nitroprusside and adenosine. 23 patients were exposed to one or more coronary risk factors. The vasoconstrictor effect of L-NMMA on the epicardial and microvessels was greater in patients free of risk factors: Coronary vascular resistance was 36% higher in patients without risks, compared to 17% higher in patients with risks (P < 0.05). Both epicardial and microvascular dilator effects of ACH were greater in patients without risk factors, and the inhibition of these effects by L-NMMA was also greater in patients without risk factors. Thus: (a) NO contributes importantly to resting epicardial and coronary microvascular tone, (b) coronary vascular dilation in response to ACH is predominantly due to increased production of NO, and (c) despite the absence of angiographic evidence of atherosclerosis, exposure to coronary risk factors is associated with reduced resting and stimulated bioavailability of NO from the human coronary circulation.
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PMID:Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis. 770 83

The recruitment of monocytes into the arterial wall is one of the earliest events in the pathogenesis of atherosclerosis. Since monocyte chemoattractant protein 1 (MCP-1) plays a key role in the subendothelial recruitment of monocytes, we tested whether nitric oxide (NO) modulates the expression of MCP-1 in cultured human endothelial cells. Inhibition of basal NO production by NG-nitro-L-arginine (L-NAG) upregulates endothelial MCP-1 mRNA expression (250 +/- 20%) and protein secretion. Exogenous addition of NO dose-dependently decreased MCP-1 mRNA expression and secretion. Changes in MCP-1 mRNA expression and protein secretion were paralleled by corresponding changes in chemotactic activity of cell-conditioned media for monocytes. An MCP-1 antibody reduced monocyte chemotactic activity by 85% and completely abolished the increased monocyte chemotactic activity induced by the inhibition of NO production. Elevation of endothelial cGMP levels had no significant effect on MCP-1 mRNA expression. Inhibition of basal endothelial NO production by L-NAG increased binding activity of a nuclear factor kappa B (NF-kappa B)-like transcriptional regulatory factor, whereas exogenous addition of NO decreased NF-kappa B-like binding activity during stimulation with tumor necrosis factor-alpha. Thus, NO modulates MCP-1 expression and monocyte chemotactic activity secreted by human umbilical vein endothelial cells (HUVECs) in culture. The activation of NF-kappa B-like transcriptional regulatory proteins by inhibition of NO suggests a molecular link between an oxidant-sensitive transcriptional regulatory mechanism and NO synthesis in HUVECs.
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PMID:Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. 775 69

To determine whether thrombin directly modifies mobility of vascular smooth muscle cells (SMC), in Transwell systems (modified Boyden chambers), we exposed SMC to alpha-thrombin. In concentrations as low as 1 NIH U/ml, thrombin induced migration as well as proliferation of SMC. Inhibition of protein synthesis by cycloheximide (2 micrograms/ml) obviated thrombin's chemotactic effect. Neither gamma-thrombin nor D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK)-inactivated alpha-thrombin (both used as controls) exerted a chemotactic effect. Concomitant hirudin or antithrombin III plus heparin inhibited chemotaxis by thrombin when added up to 2 h after addition of thrombin. alpha-Thrombin increased SMC synthesis of urokinase receptor (uPAR) and its cell surface expression as shown by metabolic labeling and immunoprecipitation as well as by flow cytometry. Thus alpha-thrombin, in concentrations thought to be present in vivo at sites of vascular injury, can stimulate not only proliferation but also migration of vascular SMC though a mechanism(s) possibly involving synthesis of uPAR, which is known to influence migration in diverse types of cells. Accordingly, both proliferation and migration dependent on thrombin may accelerate atherosclerosis, restenosis, or both after interventions such as angioplasty.
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PMID:Vascular smooth muscle cell migration mediated by thrombin and urokinase receptor. 776 12


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