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 purpose of our study was to determine the clinical, angiographic, and procedural variables that predict the risk for 2-year target lesion revascularization (TLR) and other clinical events in a large cohort of patients treated with coronary stenting. Between March 1996 and March 1999, 1,340 patients were prospectively enrolled. They underwent at least one stenting procedure with one of the four coronary stent types used during this time period in our institution: Wiktor-I, Nir, Bard XT, or Tenax. Clinical follow-up was obtained for 99.1% of eligible patients (mean, 19.38 +/- 4.97 months). The overall TLR rate was 10.7% at 24 months. Two variables were independently associated with the long-term outcome: MLD post stenting and stent type. Implantation of silicon carbide-coated stents was associated with a twofold decrease in 24-month TLR (P < 0.01). The major adverse cardiac event rate at 2 years was 20.8%. Multivariate analysis showed that three parameters were predictive: diabetes (P < 0.002), recent onset of symptoms (P < 0.03), and high diffusion of coronary atherosclerosis as assessed by Gensini score (P < 0.0069). In conclusion, stent type, and particularly passive silicon carbide coating, appears to affect the 24-month TLR rate but not other major cardiac events.
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PMID:Does stent design affect the long-term outcome after coronary stenting? 1211 81

To determine the causes and history of atherosclerosis it is necessary to understand the hemodynamic parameters of blood circulation. Hemodynamic parameters play an important role in the formation of atherosclerotic plaques, especially near bends and bifurcations where the flow separates from the wall. Here the flow is laminar and non-axial with eddies, secondary flow, flow separation and stagnation points. Stenoses are found predominantly in flow separation areas. Therefore, it is important to separately study the following flow parameters: steady and pulsatile flow, wall elasticity and non-Newtonian flow behavior of blood. A simplified silicon elastic y-model simulating the human carotid artery was used for the analysis of these parameters. This model can be used for numerical studies as well. Flow was visualized at steady flow using dyes and at pulsatile flow with a photoelastic apparatus and a birefringent solution. The local axial velocity at steady and pulsatile flow was determined with a one-component Laser-Doppler-Anemometer (LDA). Pulsatile flow was generated by a piston membrane pump. A glycerin-water solution was used to simulate the Newtonian flow behavior of blood. A DMSO-Separan water solution was used to simulate the non-Newtonian flow behavior. Pulsatile flow creates higher and lower shear rates so called oscillating shear rate compare to steady flow depending on the velocity amplitude. The non-Newtonian fluid showed a markedly different flow behavior than the Newtonian fluid especially in areas of flow separation. Shear gradients were calculated from these velocity measurements using a bicubic spline interpolation. Shear stresses were calculated from these velocity shear gradients and the viscosity of the non-Newtonian fluid at these shear gradients. At special areas, high shear stresses > 10 Pa were found. The elasticity of the model wall also influences the flow behavior. The measurements showed that the characteristics of pulsatile flow and the elasticity of the model wall should be observed concomitantly. This paper presents the steady and pulsatile flow with a Newtonian and non-Newtonian fluid in an elastic model.
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PMID:Experimental flow studies in an elastic Y-model. 1269 53

A 72-year-old male painter, who complained of his "lungs burning" for 2 weeks, died suddenly. Autopsy examination revealed severe coronary atherosclerosis with plaque rupture as the cause of death. Examination of the lungs revealed emphysema, interstitial fibrosis, and multinucleated giant cells with intra- and extracellular brown-black, crystalline, polarizable foreign material. Energy-dispersive X-ray microanalysis showed the material to contain titanium, aluminum, silicon, and iron. An increased incidence of respiratory disease has been reported in professional painters. Titanium is widely used as a pigment in the manufacturing of commercial paints. Cases of pneumoconiosis and alveolar proteinosis have been described in painters in which analysis of lung tissue revealed increased levels of titanium. This case is presented as an example of a rarely reported phenomenon, which may have clinical implications for evaluation and management of lung disease in painters.
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PMID:Titanium particles identified by energy-dispersive X-ray microanalysis within the lungs of a painter at autopsy. 1274 5

Intimal thickening, due to smooth muscle cell migration and proliferation, is considered to be one of the major components of vascular proliferative disorders such as atherosclerosis and restenosis. One experimental model, resulting in intimal thickening in the rabbit, involves placing a silicon collar around the carotid artery, and is used in this study. Endothelin is known to act as a strong mitogen and to stimulate smooth muscle cell proliferation and migration. We investigated the contribution of endothelin to the development of collar-induced intimal thickening and the effects of TAK-044, (5 mg kg(-1) daily, s.c.), a non-selective ET(A)/ET(B) receptor antagonist, on intimal thickening and vascular reactivity changes in the collared rabbit carotid artery. Endothelin levels and the intimal cross-sectional area, as well as the ratio of intimal area to media (index), increased significantly in collared arteries as compared with those in sham-operated arteries. TAK-044 significantly inhibited intimal thickening and also decreased the index without affecting increased endothelin levels in collared arteries. Vascular reactivity changes in response to collaring produced predictable effects, such as decreased contractile responses to vasoconstrictor agents and increased sensitivity to serotonin (5-hydroxytryptamine, 5-HT). In terms of contractile responses in this model, TAK-044, in particular, did not affect collar-induced vascular reactivity changes. These results suggest that endothelin may be involved in the pathogenesis of collar-induced intimal thickening. As an endothelin receptor antagonist, TAK-044 may potentially be beneficial in the treatment of atherosclerosis.
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PMID:The role of endothelin receptor antagonism in collar-induced intimal thickening and vascular reactivity changes in rabbits. 1635 4

A negative relationship between water hardness and cardiovascular mortality rate was demonstrated and became a source of interest regarding minerals and trace metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and arterial hypertension. Higher incidences of sudden death, cerebrovascular diseases, arterial hypertension, and coronary heart disease have been reported in soft water areas. A major research effort has been devoted to the problem in an attempt to find a protective factor in hard water or a detrimental factor or element in soft water. The roles of calcium, magnesium, cobalt, lithium, vanadium, silicon, manganese, and thallium [corrected] have been considered potentially beneficial, whereas those of cadmium, lead, silver, zinc, and antimony have been considered potentially harmful. Cobalt and zinc have been attributed both roles. In the present article, the role of trace quantities of several elements in mineral water in the etiopathogenesis of primary arterial hypertension is reviewed.
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PMID:Role of trace elements in primary arterial hypertension: is mineral water style or prophylaxis? 1720 82

Evaluation of mechanical environment on cellular function is a major field of study in cellular engineering. Endothelial cells lining the entire vascular lumen are subjected to pulsatile blood pressure and flow. Mechanical stresses caused by such forces determine function of arteries and their remodeling. Critical values of mechanical stresses contribute to endothelial damage, plaque formation and atherosclerosis. A device to impose cyclic strain on cultured cells inside an incubator was designed and manufactured operating with different load amplitudes, frequencies, numbers of cycles and ratios of extension to relaxation. Endothelial cells cultured on collagen coated silicon scaffolds were subjected to cyclic loading. Effects of mechanical loading on cell morphology were quantified using image processing methods. Results showed change in cell orientation from a randomly oriented before the test up to 80 degrees alignment from load axis after loading. Endothelial cells were elongated with shape index reductions up to 47% after cyclic stretch. By increase of strain amplitude, loading frequency and number of cycles, significant decrease in shape index and significant increase in orientation angle were observed. Change of load waveform similar to arterial pulse pressure waveform resulted in alteration of cell alignment with 9.7% decrease in shape index, and 10.8% increase in orientation angle. Results of cyclic loading tests in a disturbed environment with elevated PH showed lack of remodeling. It was concluded that tensile loading of endothelial cells influences cell morphology and alignment, a mechanism for structural regulation, functional adaptation and remodeling. Disturbed environment results in endothelial dysfunction and injury.
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PMID:Topological remodeling of cultured endothelial cells by characterized cyclic strains. 1843 16

Mechanical stimuli have been shown to affect cell behaviour in terms of proliferation, apoptosis, and protein expression. In terms of cardiovascular diseases, for example, endothelial and smooth muscle cells exposed to an abnormal strain environment have been associated with atherosclerosis and in-stent restenosis. The FX-4000 system (Flexercell Tension Plus System, Flexcell Corporation, McKeesport, Pennsylvania, USA) is an in-vitro system that is widely used to strain cells in order to evaluate their response to strain. The precision, accuracy, and repeatability of the strains controlled by the system are therefore crucial to analyse and interpret the results confidently. The aim of this study was to investigate the mechanical behaviour of the FX-4000 Flexercell six-well-plate silicon membranes for static and dynamic cyclic strains by measuring the maximum peak strain and analysing the change in the membrane deformation after cyclic strain for 0 h, 24 h, and 48 h at different strain amplitudes and frequencies. The results of the tests conducted demonstrate notable differences between the measured strains of the membranes in comparison with both the inputs and the outputs of the Flexcell software. The calibration method used by Flexcell International assumes that the strain values determined for a given vacuum pressure on the silicone membranes are reliable for different waveforms and frequencies. The data reported here clearly indicate that this is not the case. The results indicate that a unique calibration pressure-strain curve must be determined for each test given the viscoelastic nature of the Flexcell system. A new method to calibrate the machine in house was applied using new pressure-strain equations. This new calibration method has been presented and should enable researchers using the Flexcell machine to set up their cell experiments more accurately.
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PMID:An analysis of the strain field in biaxial Flexcell membranes for different waveforms and frequencies. 1914 17

The Tie-2 receptor has been shown to play a role in angiogenesis in atherosclerosis. The conventional method assaying the level of soluble Tie-2 (sTie-2) was ELISA. However, this method has some disadvantages. The aims of this research are to establish a more simple detection method, the optical protein-chip based on imaging ellipsomtry (OPC-IE) applying to Tie-2 assay. The sTie-2 biosensor surface on silicon wafer was prepared first, and then serum levels of sTie-2 in 38 patients with AMI were measured on admission (day 1), day 2, day 3 and day 7 after onset of chest pain and 41 healthy controls by ELISA and OPC-IE in parallel. Median level of sTie-2 increased significantly in the AMI patients when compared with the controls. Statistics showed there was a significant correlation in sTie-2 results between the two methods (r=0.923, P<0.01). The result of this study showed that the level of sTie-2 increased in AMI, and OPC-IE assay was a fast, reliable, and convenient technique to measure sTie-2 in serum.
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PMID:Soluble angiopoietin receptor Tie-2 in patients with acute myocardial infarction and its detection by optical protein-chip. 1954 32

Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been implicated in vascular cell proliferation and/or migration, contributing to intimal thickening, an essential stage in the development of atherosclerosis and restenosis following balloon angioplasty. Endothelin, a strong chemoatractant and mitogen, has been shown to promote smooth muscle cell proliferation and migration by activating MMPs via endothelin-A (ETA) receptors. The positioning of a soft silicon collar around the left carotid artery in rabbits results in intimal thickening. In this study, we investigate the possible role of gelatinases and the effect of a nonselective ETA/ETB receptor antagonist, TAK-044 (5 mg/kg body weight/day, subcutaneously [sc]), on these enzymes. Our results demonstrated that both MMP-2 and MMP-9 activities increased in response to collaring in placebo group, while treatment with TAK-044 significantly suppressed both gelatinase activities and proMMP-2 levels, and inhibited intimal thickening in collared arteries. These results suggest that either enhanced MMP expression or endothelin receptor antagonism may be involved in the formation of intimal thickening in this model.
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PMID:MMP-2 and MMP-9 alteration in response to collaring in rabbits: the effects of endothelin receptor antagonism. 1973 25

Drug carriers are generally introduced into the body intravenously and directly exposed to endothelial cells. Silica nanoparticles could be promising delivery vehicles for drug targeting or gene therapy. However, few studies have been undertaken to determine the biological behavior of silica nanoparticles on endothelial cells. Here we measured reactive oxygen species (ROS) generation, apoptosis and necrosis, proinflammatory and prothrombic properties and the levels of the apoptotic signaling proteins and the transcription factors in human umbilical vein endothelial cells (HUVECs) after exposure to silica nanoparticles of different concentrations (25, 50, 100, and 200 microg/mL) for 24h. The results showed that silica nanoparticles, ranging from 50 microg/mL to 200 microg/mL, markedly induced ROS production, mitochondrial depolarization and apoptosis in HUVECs. At the highest concentration, the necrotic rate, LDH leakage, the expression of CD54 and CD62E, and the release of TF, IL-6, IL-8 and MCP-1 were significantly increased. Silica nanoparticles also activated c-Jun N-terminal kinase (JNK), c-Jun, p53, caspase-3 and NF-kappaB, increased Bax expression and suppressed Bcl-2 protein. Moreover, inhibition of ROS attenuated silica nanoparticles-induced apoptosis and inflammation and the activation of JNK, c-Jun, p53 and NF-kappaB. In summary, our findings demonstrated that silica nanoparticles could induce dysfunction of endothelial cells through oxidative stress via JNK, p53 and NF-kappaB pathways, suggesting that exposure to silica nanoparticles may be a significant risk for the development of cardiovascular diseases such as atherosclerosis and thrombus.
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PMID:Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kappaB pathways. 2072 82


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